BACKGROUND OF THE INVENTION 
U.S. Pat. No. 3,819,683 discloses dibenzolfuryl N-methyl carbamate as an 
intermediate to be used in the preparation of an N-acylated final product 
of unknown utility. 
DESCRIPTION OF THE INVENTION 
In accordance with this invention there is provided a group of compounds of 
formula A: 
##STR2## 
wherein R.sup.1 and R.sup.2 are, independently, hydrogen, fluorine, 
chlorine, bromine, iodine, trifluoromethyl, cyano, nitro, C.sub.1 -C.sub.6 
alkyl, C.sub.1 -C.sub.6 alkoxy, --CO.sub.2 H, C.sub.2 -C.sub.7 
alkylcarbonyl, C.sub.2 -C.sub.7 alkylcarbonyloxy, C.sub.2 -C.sub.7 
alkoxycarbonyl, C.sub.2 -C.sub.7 alkoxycarbonyloxy, mono or di 
alkylaminocarbonyl in which each alkyl group has 1 to 6 carbon atoms, or 
mono or di alkylaminocarbonyloxy in which each alkyl group has 1 to 6 
carbon atoms; 
R.sup.3 is hydrogen or C.sub.1 -C.sub.6 alkyl; 
R.sup.4 is C.sub.2 -C.sub.18 alkyl, cycloalkylalkyl where the cycloalkyl 
moiety has 3 to 8 carbon atoms and the alkyl moiety has 1 to 6 carbon 
atoms or phenylalkyl of 7 to 18 carbon atoms or substituted phenylalkyl, 
where the alkyl moiety is 1 to 12 carbon atoms and the substituent on the 
benzene ring is alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon 
atoms, halo, nitro, cyano, trifluoromethyl or phenyl. 
The compounds of this invention inhibit the absorption of cholesterol from 
the intestinal tract. As indicated in Table I below, the compounds are 
inhibitors of cholesterol ester hydrolase (CEH). It has been shown that 
removal of this enzyme from pancreatic juice results in an 80% reduction 
in the uptake of cholesterol into the bloodstream in rats [Hosie et al, J. 
Biol. Chem., 262, 260 (1987)]. The association between high serum 
cholesterol levels and coronary heart disease is well documented. 
Consequently, compounds that prevent the uptake of cholesterol are useful 
for treating atherosclerosis, familial hypercholesterolemia, hyperlipemia, 
and like diseases. 
Hence, this invention also provides a method for reducing cholesterol 
uptake from the intestinal tract which comprises administering, orally or 
parenterally, to an animal in need of reduced cholesterol absorption, a 
compound of formula B: 
##STR3## 
wherein R.sup.1 and R.sup.2 are, independently, hydrogen, fluorine, 
chlorine, bromine, iodine, trifluoromethyl, cyano, nitro, C.sub.1 -C.sub.6 
alkyl, C.sub.1 -C.sub.6 alkoxy, --CO.sub.2 H, C.sub.2 -C.sub.7 
alkylcarbonyl, C.sub.2 -C.sub.7 alkylcarbonyloxy, C.sub.2 -C.sub.7 
alkoxycarbonyl, C.sub.2 -C.sub.7 alkoxycarbonyloxy, mono or di 
alkylaminocarbonyl in which each alkyl group has 1 to 6 carbon atoms, or 
mono or di alkylaminocarbonyloxy in which each alkyl group has 1 to 6 
carbon atoms; 
R.sup.3 is hydrogen or C.sub.1 -C.sub.6 alkyl; 
R.sup.4 is C.sub.1 -C.sub.18 alkyl, cycloalkylalkyl where the cycloalkyl 
moiety has 3 to 8 carbon atoms and the alkyl moiety has 1 to 6 carbon 
atoms or phenylalkyl of 7 to 18 carbon atoms or substituted phenylalkyl, 
where the alkyl moiety is 1 to 12 carbon atoms and the substituent on the 
benzene ring is alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon 
atoms, halo, nitro, cyano, trifluoromethyl or phenyl. 
In addition this invention provides pharmaceutical compositions comprising 
a compound of formula B: 
##STR4## 
wherein R.sup.1 and R.sup.2 are, independently, hydrogen, fluorine, 
chlorine, bromine, iodine, trifluoromethyl, cyano, nitro, C.sub.1 -C.sub.6 
alkyl, C.sub.1 -C.sub.6 alkoxy, --CO.sub.2 H, C.sub.2 -C.sub.7 
alkylcarbonyl, C.sub.2 -C.sub.7 alkylcarbonyloxy, C.sub.2 -C.sub.7 
alkoxycarbonyl, C.sub.2 -C.sub.7 alkoxycarbonyloxy, mono or di 
alkylaminocarbonyl in which each alkyl group has 1 to 6 carbon atoms, or 
mono or di alkylaminocarbonyloxy in which each alkyl group has 1 to 6 
carbon atoms; 
R.sup.3 is hydrogen or C.sub.1 -C.sub.6 alkyl; 
R.sup.4 is C.sub.1 -C.sub.18 alkyl, cycloalkylalkyl where the cycloalkyl 
moiety has 3 to 8 carbon atoms and the alkyl moiety has 1 to 6 carbon 
atoms or phenylalkyl of 7 to 18 carbon atoms or substituted phenylalkyl, 
where the alkyl moiety is 1 to 12 carbon atoms and the substituent on the 
benzene ring is alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon 
atoms, halo, nitro, cyano, trifluoromethyl or phenyl; 
and a pharmaceutically acceptable carder therefore. 
The compounds of this invention are conveniently prepared by one of three 
methods. In the first method the hydroxydibenzofuran is reacted with the 
appropriate isocyanate in the presence of a base in a suitable solvent 
(Scheme I). In the second method the hydroxydibenzofuran is first 
converted in situ to its chloroformate using phosgene or a phosgene 
equivalent. Reaction of the chloroformate with the desired amine in the 
presence of a base in a suitable solvent gives the desired product. A 
suitable phosgene equivalent is trichloromethyl chloroformate (Scheme II). 
In the third method the hydroxydibenzofuran is converted to the 
nitrophenyl carbonate derivative shown in Scheme III. This compound is a 
convenient intermediate since it can be isolated as a stable crystalline 
solid. Reaction of the carbonate with the appropriate amine in the 
presence of a base in a suitable solvent then gives the desired product 
(Scheme III). Specific examples of the routes illustrated in Schemes I, II 
and III are given in the Experimental Section. These specific examples are 
for illustrative purposes only and are not to be construed as limiting to 
this disclosure in any way. Those skilled in the art will be aware of 
other methods of preparing compounds of this invention. The starting 
materials or intermediates are available commercially or can be prepared 
by standard literature procedures. 
##STR5## 
The in vitro and in vivo standard experimental test procedures used to 
establish the ability of the anticholesterolemic compounds of this 
invention to prevent cholesteryl ester formation and to inhibit 
cholesterol absorption, are given below and the biological results are 
presented in Table I. 
In Vitro Test Procedure: The ability of the compounds of this invention to 
inhibit the formation of cholesteryl esters and thereby interfere with and 
prevent assimilation of cholesterol into the lymphatic system and 
ultimately the blood stream was established by incubating the compounds at 
37.degree. C. with a mixture of cholesterol and oleic acid in the presence 
of buffered cholesterol esterase [(EC 3.1.1.13) Sigma Company, St. Louis, 
Mo., U.S.A., No. C-1892, from bovine pancreas] and measuring the amount of 
ester formed, according to the procedure of Field, J. of Lipid Research, 
25, 389 (1984). The concentration of test compound that inhibits one-half 
of the ester formation (IC.sub.50) is given in Table I. 
In Vivo Assay: The in vivo cholesterol absorption studies were conducted in 
normal rats by oral administration of the compound being tested in 
propylene glycol and olive oil followed by oral administration of 
[4-.sup.14 C] cholesterol in propylene glycol and olive oil, otherwise 
following the procedure of Cayen et al., J. Lipid Res. 20, 162 (1979). The 
serum radioactivity was measured at six hours after dosing. The results of 
this study are reported in the following Table I as percent decrease 
compared to control. 
TABLE I 
______________________________________ 
In Vivo Results 
Effect on 
Absorption of 
.sup.14 C-chol-6 hr- 
In Vitro Results normal rat 
IC.sub.50 (.mu.M) 
% Decrease 
Example CEH (mg/kg) 
______________________________________ 
1 25 Not Determined 
2 3.0 33% (10) 
3 9.3 37% (10) 
4 68 44% (10) 
5 42 Not Determined 
6 13.8 43% (10) 
7 7.2 (IC.sub.25) 13% (10) 
8 18.9 18% (10) 
______________________________________

EXPERIMENTAL SECTION 
EXAMPLE 1 
Butylcarbamic acid 2-dibenzofuranyl ester 
A solution of 2-hydroxydibenzofuran (1.47 g, 7.98 mmol), butyl isocyanate 
(1.26 mL, 11.2 mmol) and triethylamine (0.89 mL, 6.39 mmol) in 50 mL of 
methylene chloride was stirred under N.sub.2 at room temperature for 1 
hour. The solvent was removed under reduced pressure to give a solid. 
Recrystallization from diethyl etherhexane gave 1.23 g (54%) of the title 
compound as a white crystalline solid, mp 124.degree.-126.degree. C. 
Elemental analysis for C.sub.17 H.sub.17 NO.sub.3 Calc'd: C, 72.10; H, 
6.00; N, 4.94 Found: C, 71.88; H, 6.03; N, 5.13 
EXAMPLE 2 
(1.5-Dimethylhexyl) carbamic acid 2-dibenzofuranyl ester 
A solution of 2-hydroxydibenzofuran (5.0 g, 27 mmol) and dimethylaniline 
(3.4 mL, 27 mmol) in 35 mL of benzene plus 1.5 mL of dioxane was added 
dropwise under nitrogen to a solution of trichloromethyl chloroformate 
(1.6 mL, 14 mmol) in 30 mL of benzene at ice bath temperature. After the 
addition the cooling bath was removed and the stirring continued for 
approximately 24 hours. The reaction was cooled to ice bath temperature 
and a solution of 1,5-dimethylhexylamine (4.6 mL, 27 mmol) and pyridine 
(4.4 mL, 54 mmol) in 30 mL of benzene was added dropwise over 15 minutes. 
After the addition the reaction was stirred at ice bath temperature for 2 
hours. The cooling bath was removed and the stirring continued for 
approximately 22 hours. The reaction was extracted two times with 1N HCl. 
The organic solution was dried over anhydrous MgSO.sub.4 and the solvent 
removed under reduced pressure to give 6.19 g of a yellow solid. 
Recrystallization from isopropanol gave 4.27 g (46%) of the title compound 
as a yellow crystalline solid, mp 114.degree.-115.degree. C. 
Elemental analysis for C.sub.21 H.sub.25 NO.sub.3 Calc'd: C, 74.31; H, 
7.42; N, 4.13 Found: C, 74.22; H, 7.50; N, 3.98 
EXAMPLE 3 
Hexylcarbamic acid 2-dibenzofuranyl ester 
A solution of 2-hydroxydibenzofuran (5.0 g, 27 mmol), hexyl isocyanate (4.1 
g, 32 mmol) and triethylamine (3.0 mL, 22 mmol) in 75 mL of methylene 
chloride was stirred under nitrogen at room temperature overnight. The 
reaction was extracted with 1N HCl. The organic solution was dried 
(MgSO.sub.4) and the solvent removed under reduced pressure to give 8.89 g 
of an off-white solid. Recrystallization of the solid from isopropanol 
gave 5.48 g (65%) of the title compound as an off-white crystalline solid, 
mp 109.degree.-110.degree. C. 
Elemental analysis for C.sub.19 H.sub.21 NO.sub.3 Calc'd: C, 73.29; H, 
6.80; N, 4.50 Found: C, 73.12; H, 6.79; N, 4.48 
EXAMPLE 4 
(4-Phenylbutyl)carbamic acid 2-dibenzofuranyl ester 
A solution of 2-hydroxydibenzofuran (5.0 g, 27 mmol) and dimethylaniline 
(3.4 mL, 27 mmol) in 35 mL of tetrahydrofuran plus 1.5 mL of dioxane was 
added dropwise under nitrogen to a solution of trichloromethyl 
chloroformate (1.6 mL, 14 mmol) in 30 mL of tetrahydrofuran at ice bath 
temperature. After the addition the cooling bath was removed and the 
stirring continued for approximately 24 hours. The reaction was cooled to 
ice bath temperature and a solution of 4-phenylbutylamine (4.3 mL, 27 
mmol) and pyridine (4.4 mL, 54 mmol) in 30 mL of tetrahydrofuran was added 
dropwise over 15 minutes. After the addition the reaction was stirred at 
ice bath temperature for 2 hours. The cooling bath was removed and the 
stirring continued for approximately 22 hours. The reaction was diluted 
with ethyl acetate, extracted two times with 1N HCl, dried (MgSO.sub.4) 
and the solvent removed under reduced pressure to give 6.47 g of a yellow 
solid. Purification of the solid by chromatography on silica gel (230-400 
mesh) using hexane-methylene chloride as the eluent gave 1.28 g (13%) of 
the title compound as a white crystalline solid, mp 
113.degree.-114.degree. C. 
Elemental analysis for C.sub.23 H.sub.21 NO.sub.3 Calc'd: C, 76.86; H, 
5.89; N, 3.90 Found: C, 76.74; H, 6.03; N, 3.85 
EXAMPLE 5 
Methylcarbamic acid 2-dibenzofuranyl ester 
A solution of 2-hydroxydibenzofuran (5.0 g, 27 mmol), methyl isocyanate 
(1.9 mL, 32 mmol) and triethylamine (3.0 mL, 22 mmol) in 75 mL of 
methylene chloride was stirred under nitrogen at room temperature 
overnight. During this time a solid formed. Additional methylene chloride 
was added and the solid dissolved. The reaction was then extracted with 1N 
HCl, dried (MgSO.sub.4) and the solvent removed under reduced pressure to 
give 5.47 g of a yellow solid. Recrystallization from isopropyl ether gave 
3.43 g (52%) of the title compound as a light brown crystalline solid, mp 
155.degree.-156.degree. C. 
Elemental analysis for C.sub.14 H.sub.11 NO.sub.3 Cal'd: C, 69.70; H, 4.60; 
N, 5.81 Found: C, 69.90; H, 4.90; N, 5.13 
EXAMPLE 6 
(Cyclohexylmethyl)carbamic acid 2-dibenzofuranyl ester 
In the same manner as described in Example 4, and replacing 
4-phenylbutylamine with cyclohexylmethylamine, the title compound was 
produced as a white crystalline solid (0.832 g, 9% ) after purification of 
the crude reaction product on silica gel using hexane-ethyl acetate as the 
eluent and recrystallization of the material isolated from ethyl acetate, 
mp 162.degree.-163.degree. C. 
Elemental analysis for C.sub.20 H.sub.21 NO.sub.3 Cal'd: C, 74.28; H, 6.54; 
N, 4.33 Found: C, 74.40; H, 6.86; N, 4.35 
EXAMPLE 7 
Dodecylcarbamic acid 2-dibenzofuranyl ester 
A solution of 2-hydroxydibenzofuran (25 g, 0.136 mol) and pyridine (11 mL, 
0.136 mol) in 300 mL of methylene chloride was added under nitrogen 
dropwise over five hours to a solution of 4-nitrophenyl chloroformate 
(27.4 g, 0.136 mol) in 300 mL of methylene chloride at ice bath 
temperature. After the addition the reaction was stirred at room 
temperature overnight. The solid formed was collected by filtration to 
give 33.08 g of a light tan solid. The filtrate was extracted one time 
with 1N HCl, one time with saturated Na.sub.2 CO.sub.3 (emulsion formed), 
dried (MgSO.sub.4) and the solvent removed under reduced pressure to give 
an additional 14.30 g of a light tan solid. This solid was triturated two 
times with methylene chloride to give 7.39 g of a light tan solid which 
was combined with the original 33.08 g of solid. Recrystallization of the 
combined material from ethyl acetate gave 20.23 g (43%) of carbonic acid 
(4-nitrophenyl) ester (2-dibenzofuranyl) ester as a light tan crystalline 
solid, mp 183.degree.-185.degree. C. 
Elemental analysis for C.sub.19 H.sub.11 NO.sub.6 Cal'd: C, 65.33; H, 3.17; 
N, 4.01 Found: C, 65.11; H, 3.32; N, 3.94 
A solution of the carbonate (2.0 g, 5.73 mmol), produced in the preceding 
paragraph, in 100 mL of chloroform (ethanol free) was added under nitrogen 
dropwise over 2 hours to a solution of dodecylamine (1.2 g, 6.47 mmol) and 
triethylamine (4.0 mL, 28.7 mmol) in 25 mL of chloroform at room 
temperature. After the addition the reaction was stirred overnight at room 
temperature. The reaction was extracted with 1N HCl, multiple times with 
saturated sodium carbonate, dried (MgSO.sub.4) and the solvent removed 
under reduced pressure to give 2.28 g of an off-white solid. 
Recrystallization of this solid from methylene chloride-diisopropyl ether 
gave 1.31 g (58%) of the title compound as a white crystalline solid, mp 
112.degree.-114.degree. C. 
Elemental analysis for C.sub.25 H.sub.33 NO.sub.3 Cal'd: C, 75.92; H, 8.41; 
N, 3.54 Found: C, 75.59; H, 8.74; N, 3.80 
EXAMPLE 8 
Ethylcarbamic acid 2-dibenzofuranyl ester 
In the same manner as described in Example 7, and replacing dodecylamine 
with ethylamine, the title compound was produced as a white crystalline 
solid (0.63 g, 43%) after recrystallization of the crude reaction mixture 
from methylene chloride-diisopropyl ether, mp 141.degree.-144.degree. C. 
Elemental analysis for C.sub.15 H.sub.13 NO.sub.3 Cal'd: C, 70.58; H, 5.13; 
N, 5.49 Found: C, 70.48; H, 5.19; N, 5.43