Method of fluorinating by using N-fluoropyridinium pyridine heptafluorodiborate

The present invention provides a novel compound represented as ##STR1## The present novel compound is prepared by reacting fluorine with pyridine-boron trifluoride and is useful as a fluorinating agent in the fluorination of organic compounds.

This invention relates to N-fluoropyridinium pyridine heptafluorodiborate. 
Many fluorinating reagents are known in the art. One type of fluorinating 
reagent is known as electrophilic fluorinating reagents. This type of 
fluorinating reagent is characterized by a structure containing an O-F or 
N-F bond. Electrophilic fluorinating reagents having an N-F bond include 
1-fluoro-2-pyridone as taught by S. T. Purrington et al., 
"1-Fluoro-2-pyridone: A Useful Fluorinating Reagent", J. Qrg. Chem. 48, 
761 (1983); N-fluoro-N-alkylsulfonamides as taught by W. E. Barnette, 
"N-Fluoro-N-alkylsulfonamides: Useful Reagents for the Fluorination of 
Carbanions", J. Am. Chem. Soc. 106, 452 (1984); N-fluoroquinuclidinium 
fluoride as taught by R. E. Banks et al., "Electrophilic Fluorination with 
N-fluoroquinuclidinium Fluoride", J. of Fluorine Chem. 32, 461 (1986); and 
N-fluoropyridinium salts as taught by T. Umemoto et al., 
"N-fluoropyridinium Triflate and its Analogs, The First Stable 1:1 Salts 
of Pyridine Nucleus and Halogen Atom", Tetrahedron Letters 27(28), 3271 
(1986). 
N-fluoropyridinium salts have been shown to be stable fluorinating reagents 
with the ability to fluorinate a variety of organic compounds. For 
example, T Umemoto et al., "N-fluoropyridinium Triflate and Its 
Derivatives: Useful Fluorinating Agents", Tetrahedron Letters 27(37), 4465 
(1986) report that these salts are useful in the fluorination of aromatic 
compounds and the conversion of enol silyl ethers to alpha-fluoroketones. 
T. Umemoto et al., "Base-Initiated Reactions of N-fluoropyridinium Salts; 
A Novel Cyclic Carbene Proposed as a Reactive Species", Tetrahedron 
Letters 28(24), 2705 (1987) report that N-fluoropyridinium salts can also 
be converted into useful pyridine derivatives such as 2-chloropyridine. 
However, N-fluoropyridinium salts are disadvantageous because the current 
method for their preparation is hazardous. As taught by the aforementioned 
first Umemoto et al. article, fluorine is first reacted with pyridine or a 
substituted pyridine at low temperature to give a pyridine difluoride. In 
a second step, the pyridine difluoride is converted into an 
N-fluoropyridinium salt. N-fluoropyridinium tetrafluoroborate and its 
method of preparation are shown below: 
##STR2## 
See also European Patent Application Publication 204,535. As those skilled 
in the art know, pyridine difluorides are inherently unstable and have 
been known to decompose violently even at temperatures below 0.degree. C. 
If the foregoing preparation method were used on a large scale, the 
formation of pyridine difluoride, even if temporary, would be extremely 
hazardous 
In response to the foregoing hazard, we attempted to prepare 
N-fluoropyridinium tetrafluoroborate without the formation of isolable 
quantities of pyridine difluoride by reacting fluorine with pyridine-boron 
trifluoride complex. The resulting product was totally unexpected. 
SUMMARY OF THE INVENTION 
The resulting product is a novel compound represented as 
##STR3## 
This novel compound will be referred to as N-fluoropyridinium pyridine 
heptafluorodiborate. In contrast to the N-fluoropyridinium 
tetrafluoroborate taught by the aforementioned first Umemoto et al. 
article, the present compound has an additional pyridine ring therein and 
a heptafluorodiborate group rather than a tetrafluoroborate group. Also, 
Umemoto et al. report that N-fluoropyridinium tetrafluoroborate has a 
melting point of 90.degree.-91.degree. C. while the present novel compound 
has a melting point of 196.degree.-197.degree. C. 
The present compound is useful as a fluorinating agent and is less 
expensive than the currently used fluorinating agent, N-fluoropyridinium 
triflate. Other advantages of the present compound are that the 
preparation hazards associated with pyridine difluoride intermediates are 
eliminated and the present compound can be prepared at more convenient 
temperatures. 
It should be noted that during our attempt to prepare N-fluoropyridinium 
tetrafluoroborate based salts without the formation of isolable quantities 
of pyridine difluoride, we reacted fluorine with 
3,5-dichloropyridine-boron trifluoride complex. As expected based on the 
teachings of the aforementioned Umemoto et al. article, 
3,5-dichloro-N-fluoropyridinium tetrafluoroborate formed as shown in 
Example 45 of the aforementioned European Patent Application; a 
chlorinated version of the present compound did not form. This further 
demonstrates the unexpectedness of the present N-fluoropyridinium pyridine 
heptafluorodiborate. 
Other advantages of the present invention will become apparent from the 
following description and appended claims. 
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
The present N-fluoropyridinium pyridine heptafluorodiborate is prepared by 
reacting fluorine with pyridine-boron trifluoride dissolved in a solvent 
at a temperature of about -40.degree. to about +35.degree. C. Commercially 
available pyridine-boron trifluoride may be used to prepare the present 
compound or pyridine-boron trifluoride complex may be prepared by simply 
passing BF.sub.3 over pyridine. 
A solvent which will dissolve appreciable amounts of pyridine-boron 
trifluoride, is inert to fluorine, and is unreactive towards the product 
is useful herein. An example of a useful solvent is acetonitrile. 
Preferably, the solvent is commercially available acetonitrile. 
Preferably, the dissolved pyridine-boron trifluoride is at a temperature of 
about -25.degree. to about +25.degree. C., and more preferably, about 
-5.degree. to about +25.degree. C. 
Commercially available fluorine is then bubbled into the solution. For 
safety reasons, it is advantageous to dilute the fluorine with 
commercially available nitrogen. Based on the amount of nitrogen used, the 
amount of fluorine used may be about 5 to 35 percent by volume and more 
specifically, about 10 to 20 percent by volume. Typically, about 1 mole 
equivalent of fluorine is added to the pyridine-boron trifluoride in 
acetonitrile. Adding more than 1 mole equivalent of fluorine wastes the 
fluorine while adding less then 1 mole equivalent of fluorine wastes the 
pyridine-boron trifluoride. 
As reported in present Example 1, seven grams of pyridine-boron trifluoride 
were dissolved in 50 ml acetonitrile and reacted with fluorine to give a 
product yield of 66%. We then found that upon scale-up, the use of larger 
quantities of pyridine-boron trifluoride resulted in poorer yields. 
We then accidently found that product yields are unexpectedly improved by 
running the present reaction in the presence of water. Because 
commercially available solvent may have water therein, the solvent may 
serve as a source of water. For example, one sample of commercially 
available acetonitrile contained 0.22% water by weight or about 170 
microliters of water in 100 cc of acetonitrile. Another sample of 
commercially available acetonitrile contained 0.005% by weight or about 4 
microliters of water in 100 cc of acetonitrile. If the solvent contains 
insufficient water or does not contain any water, water will then have to 
be added in order to arrive at the total amount of water required as 
described below. 
As such, preferably the fluorine is reacted with the pyridine-boron 
trifluoride dissolved in solvent in the presence of water. Preferably the 
total amount of water present is about 2 to about 12 microliters per gram 
of starting pyridine-boron trifluoride. The use of greater than about 20 
microliters of water per gram of starting pyridine-boron trifluoride 
causes the precipitation of pyridinium tetrafluoroborate salt which does 
not lead to the desired product and also contaminates the desired product. 
More preferably, the total amount of water present is about 3 to about 8 
microliters per gram of starting pyridine-boron trifluoride, and most 
preferably, about 4 to about 6 microliters per gram. 
The water may be added to the reaction mixture in several different ways. 
For example, the water may be added to the pyridine-boron trifluoride 
dissolved in solvent prior to reaction with the fluorine; this method of 
water addition is undesirable because precipitation of the pyridinium 
tetrafluoroborate salt may occur. As another example, a stream of nitrogen 
or air may be bubbled through water and then the wet gas may be passed 
into the reactor to continuously supply a steady but very low supply of 
water; the flow rate of the wet gas is adjusted to supply the required 
amount of water based on the starting pyridine-boron trifluoride in the 
reactor and the reaction rate as dictated by the fluorine mass flow rate. 
In another method which is preferred, the water is incrementally added to 
the reaction mixture and the rate of the incremental water addition is 
determined by the fluorine mass flow rate; such incremental additions may 
be done continuously or intermittently. Most preferably, the amount of 
each incremental addition is about 0.3 to about 2.0 microliters of water 
per gram of starting pyridine-boron trifluoride. 
We have also found that the N-fluoropyridinium pyridine heptafluorodiborate 
product is less soluble than pyridine-boron trifluoride in acetonitrile. 
If the ratio of pyridine-boron trifluoride to acetonitrile is too great, 
the product comes out of solution and interferes with the fluorine flow 
and thus the reaction. Preferably, the ratio of grams of pyridine-boron 
trifluoride to cc of acetonitrile does not exceed 0.8. 
The fluorine uptake may be conveniently monitored by passing the gas 
effluent from the reactor through a bubbler containing a solution of 
potassium iodide in water. If the fluorine uptake ceases, the fluorine 
passes through the reactor and immediately reacts with the potassium 
iodide in the bubbler liberating iodine which turns the almost colorless 
solution a dark brown. 
The N-fluoropyridinium pyridine heptafluorodiborate is useful as a 
fluorinating agent. This compound is useful in fluorinating organic 
compounds including aliphatic compounds such as 1-octyl magnesium bromide 
and enolate derivatives such as 3-pentanone enol acetate; alicyclic 
compounds such as 1-morpholino-1-cyclohexene, 1-morpholino-1-cyclopentene, 
2-carboethoxy cyclopentanone and cyclohexanone trimethyl silyl enol ether; 
and aromatic compounds such as benzene and anisole. 
Activated olefins of Formula (I) below can be fluorinated 
##STR4## 
or Formula (II) 
##STR5## 
wherein A is selected from the group consisting of --OCOR, --OR, 
--OSiR.sub.3, --NCOR, and NR.sub.2 wherein R is an alkyl group having 1 to 
6 carbon atoms. Examples of activated olefins are set forth in Table 1 
below. In Table 1, F(I) means Formula (I) and F(II) means Formula (II). 
TABLE I 
______________________________________ 
F(I) F(II) A Name 
______________________________________ 
X -- OCOCH.sub.3 1-acetoxy-1-cyclohexene 
X -- OCH.sub.3 1-methoxy-1-cyclohexene 
X -- OSi(CH.sub.3).sub.3 
1-cyclohexenyloxy- 
trimethylsilane 
X -- NCOCH.sub.3 1-acetamino-1-cyclohexene 
X -- 
##STR6## 1-pyrrolidino-1-cyclohexene 
-- X OCOCH.sub.3 6-acetoxy-1,2,3,7,8,8a- 
hexahydronaphthalene 
-- X OCH.sub.3 1,2,3,7,8,8a-hexahydro-6- 
methoxynaphthalene 
-- X OSi(CH.sub.3).sub.3 
1,2,3,7,8,8a-hexahydro-6- 
trimethyloxysilylnaphthalene 
-- X NCOCH.sub.3 6-acetamino-1,2,3,7,8,8a- 
hexahydronaphthalene 
-- X 
##STR7## 1,2,3,7,8,8a-hexahydro-6- pyrrolidinonaphthalene 
______________________________________ 
Organic sulfides which can be fluorinated are represented by Formula (III) 
EQU RSCH.sub.2 R' 
wherein R is selected from the group consisting of an alkyl group having 1 
to 6 carbon atoms and an aryl group having 6 to 10 carbon atoms and R' is 
selected from the group consisting of hydrogen, an alkyl group having 1 to 
6 carbon atoms, an ester group having 2 to 7 carbon atoms, and a ketone 
having 2 to 7 carbon atoms. 
When an activated olefin of the Formula (I) above is being fluorinated, the 
fluorine adds to the 2-position of the ring. Although not wishing to be 
bound by theory, we believe that the fluorine adds to the ring by a 
one-electron transfer mechanism as taught by Umemoto et al. 
When an activated olefin of the Formula (II) above is being fluorinated, 
the fluorine adds to the 4-position of the ring. Although not wishing to 
be bound by theory, we believe that the fluorine adds to the ring by 
one-electron transfer mechanism as taught by Umemoto et al. 
When a sulfide of the Formula (III) is being fluorinated, the fluorine 
replaces one of the hydrogens adjacent to the sulfur atom. Although not 
wishing to be bound by theory, we believe that alpha-fluorination of 
sulfides occurs via oxidative fluorination of the sulfur followed by 
rearrangement of fluorine to the alpha-carbon. 
Fluorinated aliphatic compounds are useful in many applications including 
pharmaceuticals while fluorinated aromatic compounds are useful in many 
applications including chemical intermediates for pharmaceutical and 
agricultural compounds. 
As such, the present invention provides a method of fluorinating organic 
compounds by using N-fluoropyridinium pyridine heptafluorodiborate as a 
fluorinating agent. The method of fluorinating an organic compound 
involves reacting the N-fluoropyridinium pyridine heptafluorodiborate with 
the organic compound in a solvent at a temperature sufficient to effect 
the fluorination. Preferably, the solvent is methylene chloride or 
acetonitrile. 
The fluorination temperature is about 0.degree. C. to about 100.degree. C. 
Preferably, the temperature is about 70.degree. C. to about 90.degree. C. 
for the fluorination of enol acetates and about 0.degree. C. to about 
10.degree. C. for the fluorination of trimethylsilyl enol ethers. 
Preferably, the temperature is about 15.degree. C. to about 35.degree. C. 
for the fluorination of the other above-identified activated olefins and 
sulfides.

The present invention is more fully illustrated by the following 
non-limiting Examples. 
EXAMPLE 1 
Example 1 is directed to the preparation of N-fluoropyridinium pyridine 
heptafluorodiborate. 
Pyridine-boron trifluoride complex (7 g, 0 0477 mol) was dissolved in 50 mL 
acetonitrile at ice bath temperature. Fluorine (8 cc/min) diluted with 
nitrogen (68 cc/min) was bubbled in for 3 hours (0.054 mol fluorine). 
After the addition was complete, the solution was triturated with carbon 
tetrachloride and cooled to give 5.2 g of a peach-colored solid. 
Recrystallization from acetone gave tan crystals, mp 196.degree.-7.degree. 
C. Anal. Calcd. for C.sub.10 H.sub.10 B.sub.2 F.sub.8 N.sub.2 : C, 36.20, 
H, 3.04; N, 8.44; Found: C, 36.75; H, 3.39; N, 8.06. Molecular weight by 
iodometric titration, Calcd.: 331.6; Found: 323. .sup.19 F NMR: 48.2 
downfield from CFCl.sub.3 (1 F) and 150.1 ppm upfield from CFCl.sub.3 (7 
F); .sup.1 H NMR (CH.sub.3 CN): 9.24 (dd, 2H), 8.5-8.8 (m, 4H), 7.9-8.4 
(m, 4H) ppm; .sup.11 B NMR: -0.12 ppm relative to NH.sub.4 BF.sub.4 ; 
.sup.13 C NMR 148.8, 148.0, 142.7, 137.3, 131.3 and 128.8 ppm. 
Examples 2-9 are directed to the fluorination of various organic compounds 
by using N-fluoropyridinium pyridine heptafluorodiborate as a fluorinating 
agent. 
EXAMPLE 2 
The reagent (0.25 g) from Example 1 and 2 mL benzene were refluxed in 15 mL 
methylene chloride overnight. The presence of fluorobenzene was indicated 
by GC-MS. 
EXAMPLE 3 
Anisole (0.1 g) and 0.25 g of the reagent from Example 1 were refluxed in 
CH.sub.2 Cl.sub.2. After 7 hours, 20% of the anisole was converted to a 
1:1 mixture of 2-fluoro-and 4-fluoroanisole. After 24 hours reflux, the 
conversion was 70%. 
EXAMPLE 4 
The fluorinating reagent prepared according to Example 1 (9.95 g, 30 mmol) 
dissolved in 40 mL dry acetonitrile is added slowly to a solution of 
1-morpholino-1-cyclohexene (3.35 g, 20 mmol) in 15 mL acetonitrile at a 
rate to maintain a temperature of less than 35.degree. C. The mixture is 
then stirred at room temperature for an additional six hours. Aqueous 2 N 
HCl (25 mL) is added and the mixture refluxed for one hour. The cooled 
mixture is diluted with 50 mL water and extracted three times with 35 mL 
methylene chloride. The combined organic layers are dried (MgSO.sub.4) and 
solvent removed to leave a residue containing 3-fluorocyclohexanone which 
is purified chromatographically. 
EXAMPLES 5-9 
The following organic compounds and 0.25 g of the reagent from Example 1 
are refluxed in methylene chloride, except for Example 9 where the 
reaction is carried out at room temperature in tetrahydrofuran, to prepare 
fluorinated organic compounds. 
______________________________________ 
Example Organic Compound 
______________________________________ 
5 1-morpholino-1-cyclopentene 
6 2-carboethoxy cyclopentanone 
7 cyclohexanone trimethyl silyl enol ether 
8 3-pentanone enol acetate 
9 1-octyl magnesium bromide 
______________________________________ 
Examples 2-9 show that the reagent fluorinates aromatic and aliphatic 
compounds. 
EXAMPLE 10 
This Example provides additional chemical evidence for the existence of an 
N-fluoropyridium cation in the present compound. 
The fluorinating reagent (0.5 g) from Example 1 was refluxed for 1 hour in 
5 mL acetonitrile containing 1 g KF. From the reaction mixture, pyridine, 
2-fluoropyridine, and 2-acetamidopyridine were identified by GC-MS. The 
latter two products are consistent with the behavior of N-fluoropyridinium 
salts as reported by Umemoto et al. "Preparation of 2-Fluoropyridines via 
Base - Induced Decomposition of N-Fluoropyridinium Salts", J. Org. Chem. 
54, 1726 (1989). 
COMATIVE 
This Comparative illustrates the advantage of adding water during the 
reaction of the fluorine and the pyridine-boron trifluoride in scale-up in 
improving product yield. 
To a reactor, 80.0 g of pyridine-boron trifluoride and 320 ml of 
acetonitrile were charged and purged with N.sub.2. The reactor was placed 
in an ice-bath and a mixture of 10% F.sub.2 in N.sub.2 (V/V) was bubbled 
into the stirred solution at a rate of 200 cc/min. After nearly three 
hours of addition, the exhaust gases from the reaction turned the 
potassium iodide trap to a dark color which indicated that the reaction 
was not absorbing F.sub.2. The reactor contents were cooled and carbon 
tetrachloride was added; this addition precipitated white crystals (CROP 
1). These crystals were collected and vacuum dried at 25.degree. C. for 
several hours (melting point: 192.degree.-194.degree. C.). .sup.1 H and 
.sup.19 F-NMR showed the presence of product. To the filtrate from CROP 1 
above, more carbon tetrachloride was added which precipitated a second 
crop(CROP 2) of crystals. These crystals were collected and dried as above 
to give a solid with a melting point: 194.degree.-197.degree. C. and again 
.sup.1 H and .sup.19 F-NMR showed presence of product. The total yield of 
CROP 1 and CROP 2 was 24.9%. 
EXAMPLE 11 
To a reactor, 80.0 g pyridine-boron trifluoride complex and 300 ml of 
acetonitrile were charged and purged with N.sub.2. The reactor was placed 
in an ice-bath and a mixture of 10% F.sub.2 in N.sub.2 (V/V) was bubbled 
through the stirred solution at a rate of 200 cc/min. After 2.5 hours, the 
exhaust gases from the reaction turned potassium iodide solution dark 
which indicated that F.sub.2 was no longer being absorbed. 100 microliters 
of water were then added and fluorination was resumed with a fresh 
potassium iodide trap in place. The reaction absorbed F.sub.2 for 1.5 
hours at which point, the trap darkened. 50 microliters of water were 
added to the reaction and fluorination was resumed. In 0.5 hour, F.sub.2 
was no longer being absorbed. Two more additions of 50 microliters of 
water each were made, each time with subsequent F.sub.2 addition and 
absorption. The reaction liquor was cooled and R-113 added to precipitate 
near white crystals which were vacuum dried at 25.degree. C. for several 
hours. For CROP 1, the yield was 47.3 g or 52.4% with a melting point of 
192.degree.-194.degree. C. The filtrate was rotovapped to give a second 
crop of crystals which were filtered and vacuum dried. The yield was 27.0 
g with a melting point of 150.degree.-180.degree. C. .sup.1 H and .sup.19 
F-NMR verified the product in both CROPS. CROP 2 showed some impurities. 
Examples 12 through 18 are directed to the fluorination of various organic 
compounds by using N-fluoropyridinium pyridine heptafluorodiborate as a 
fluorinating agent. 
EXAMPLE 12 
This Example is directed to the fluorination of 
3,17beta-diacetoxy-3,5-androstadiene to produce 6-fluorotestosterone 
acetate. 
We prepared 3,17beta-diacetoxy-3,5-androstadiene by using the procedure of 
Chavis, C.; Mousseron-Canet, M. Bull. Soc. Chim. France (1971), 632. 
To a solution of 3,17beta-diacetoxy-3,5-androstadiene (100 milligrams, 0.27 
millimole) in acetonitrile (0.6 milliliter) was added N-fluoropyridinium 
pyridine heptafluorodiborate (98 milligrams, 0.30 millimole) and the 
reaction stirred at 40.degree. C. for 2 days. The mixture was poured into 
ether (10 milliliters), filtered through anhydrous MgSO.sub.4 and 
evaporated to afford 90 milligrams (96% yield) of a 1 to 1.1 ratio of 6 
alpha- to 6 beta-fluorotestosterone acetate. 
EXAMPLE 13 
This Example is directed to the fluorination of 3,17beta-bistrimethyl 
siloxy-3,5androstadiene to produce 
6-fluoro-17beta-trimethylsiloxytestosterone. 
We prepared 3,17beta-bistrimethylsiloxy-3,5-androstadiene by using the 
procedure of Paterson, I; Price, L. G. Tetrahedron Letters (1981) 22, 
2833. 
To a solution of 3,17beta-bistrimethylsiloxy-3,5-androstadiene (150 
milligrams, 0.35 millimole) in acetonitrile (1.4 millimeters) was added 
N-fluoropyridinium pyridine heptafluorodiborate (127 milligrams, 0.38 
millimole) and the reaction stirred at room temperature for 18 hours. The 
mixture was poured into ether (10 milliliters), filtered through anhydrous 
MgSO.sub.4 and evaporated to afford 111 milligrams (88% yield) of a 1 to 3 
ratio of 6 alpha- to 6 beta-fluoro-17 beta-trimethylsiloxytesterone. 
EXAMPLE 14 
This Example is directed to the fluorination of 
1-acetoxy-4-t-butylcyclohexene to produce 2-fluoro-4-t-butylcyclohexanone. 
We prepared 1-acetoxy-4-t-butylcyclohexene by using the procedure of House, 
H. O.; Tefertiller, B. A.; Olmstead, H. D. J. Org. Chem. (1968) 33, 935. 
To a solution of 1-acetoxy-4-t-butylcyclohexene (1 gram, 5.1 millimoles) in 
acetonitrile (5 milliliters) was added N-fluoropyridinium pyridine 
heptafluorodiborate (3.10 grams, 9.4 millimoles) in acetonitrile (10 
milliliters) and the reaction refluxed for 18 hours. The mixture was 
poured into ether (75 milliliters), filtered through anhydrous MgSO.sub.4 
and evaporated. The residue was chromatographed on silica gel to afford 
0.4 gram. (62% yield) of a 2.5 to 1 ratio of cis- to 
trans-2-fluoro-4-t-butylcyclohexanone. 
EXAMPLE 15 
This Example is directed to the fluorination of enol-acetate of 
alpha-tetralone to produce 2-fluoro-alpha-tetralone. 
We prepared the enol-acetate of alpha-tetralone according to the procedure 
of Rozen, S.; Menahem, Y. J. Fluorine Chem. (1980) 16, 19. 
To a solution of the enol-acetate of alpha-tetralone (1 gram, 5.3 
millimoles) in acetonitrile (5.3 milliliters) was added N-fluoropyridinium 
pyridine heptafluorodiborate (3.53 grams, 10.6 millimoles) in acetonitrile 
(10 milliliters) and the reaction refluxed for 18 hours. The mixture was 
poured into ether (75 milliliters), filtered through anhydrous MgSO.sub.4 
and evaporated. The residue was chromatographed on silica gel to afford 
0.53 gram (61% yield) of 2-fluoro-alpha-tetralone. 
EXAMPLE 16 
This Example is directed to the fluorination of 
1-cyclohexenyloxytrimethylsilane to produce 2-fluorocyclohexanone. 
We purchased 1-cyclohexenyloxytrimethylsilane from Aldrich Chemical Co. 
To a solution of 1-cyclohexenyloxytrimethylsilane (1 gram, 5.9 millimoles) 
in acetonitrile (6 milliliters) was added N-fluoropyridinium pyridine 
heptafluorodiborate (2.14 grams, 6.45 millimeters) and the reaction 
stirred for 1 hour at 0.degree. C. The mixture was poured into ether (75 
milliliters), filtered through anhydrous MgSO.sub.4 and evaporated. The 
residue was chromatographed on silica gel to afford 0.25 gram (37% yield) 
of 2-fluorocyclohexanone. 
EXAMPLE 17 
This Example is directed to the fluorination of 3 
beta-acetoxy-17-acetamino-5,16-androstadiene to produce 
16-fluoro-3beta-acetoxy-5-androsten-17-one. 
We prepared 3beta-acetoxy-17-acetamino-5,16-androstadiene by using 
procedure of Rosenkranz, G.; Mancera, O.; Sondheimer, F.; Djerassi, C. J. 
Org. Chem. (1956) 21, 520. 
To a solution of 3beta-acetoxy-17-acetamino-5,16-androstadiene (150 
milligrams, 0.40 millimole) in acetonitrile (0.8 milliliters) was added 
N-fluoropyridinium pyridine heptafluorodiborate (150 milligrams, 0.44 
millimole) and the reaction stirred at room temperature for 5 days. The 
mixture was then diluted with 10% HCl (1 milliliter) and stirred for an 
additional 18 hours. Next, the solution was extracted with ether 
(3.times.1 milliliter), the combined organic layers filtered through 
anhydrous MgSO.sub.4 and evaporated to afford 115 milligrams (82% yield) 
of a 15 to 1 ratio of 16 alpha- to 16 
beta-fluoro-3beta-acetoxy-5-androsten-17-one. 
EXAMPLE 18 
This Example is directed to the fluorination of p-chlorophenyl methyl 
sulfide to produce fluoromethyl p-chlorophenyl sulfide. 
We purchased p-chlorophenyl methyl sulfide from American Tokyo Kasei, Inc. 
To a solution of p-chlorophenyl methyl sulfide (100 milligrams, 0.63 
millimole) in acetonitrile (1 milliliter) was added N-fluoropyridinium 
pyridine heptafluorodiborate (210 milligrams, 0.63 millimole) and the 
reaction stirred at room temperature for 18 hours. The mixture was poured 
into ether (10 milliliters), filtered through anhydrous MgSO.sub.4 and 
evaporated to afford a mixture of starting material and fluoromethyl 
p-chlorophenyl sulfide (26% by NMR). 
Having described the invention in detail and by reference to preferred 
embodiments thereof, it will be apparent that modifications and variations 
are possible without departing from the scope of the invention defined in 
the appended claims.