Propanolamine derivatives of the formula ##STR1## wherein R.sup.1 is hydrogen or a group of formula ##STR2## n is the number 0 or 1; R.sup.2 and R.sup.5 are phenyl, m-halophenyl, m-trifluoromethylphenyl, thienyl or pyridyl; PA1 R.sup.3 is hydrogen or methyl; PA1 R.sup.4 is hydrogen, --CH.sub.2 COOH, --CH.sub.2 COO--C.sub.1-4 -alkyl, --(CH.sub.2).sub.2 O--C.sub.1-4 -alkyl or --(CH.sub.2).sub.2 O(CH.sub.2).sub.1-4 --C.sub.6 H.sub.5 ; PA1 and a physiologically compatible salt thereof. The invention also relates to processes for the preparation of these propanolamine derivatives, pharmaceutical preparations and feedstuffs containing them, and methods of using the propanolamine derivatives.

FIELD OF THE INVENTION 
The present invention is concerned with novel propanolamine derivatives 
which are useful for the treatment of obesity of diabetes mellitus and of 
conditions which are associated with high protein breakdown. Furthermore, 
the novel propanolamine derivatives may be incorporated into feedstuffs 
for fattening animals. 
SUMMARY OF THE INVENTION 
The propanolamine derivatives of the present invention are compounds of 
formula 
##STR3## 
wherein R.sup.1 is hydrogen or a group of formula 
##STR4## 
n is the number 0 or 1; R.sup.2 and R.sup.5 are phenyl, m-halophenyl, 
m-trifluoromethylphenyl, thienyl or pyridyl; 
R.sup.3 hydrogen or methyl; 
R.sup.4 is hydrogen, --CH.sub.2 COOH, --CH.sub.2 COO-C-.sub.1-4 -alkyl, 
--(CH.sub.2).sub.2 O--C.sub.1-4 -alkyl or --(CH ).sub.2 
O(CH.sub.2).sub.1-4 -C.sub.6 H.sub.5 ; 
and a physiologically compatible salt thereof. 
The invention also relates to processes for the preparation of these 
propanolamine derivatives, pharmaceutical preparations and feedstuffs 
containing the derivatives, and methods of using the propanolamine 
derivatives. 
DETAILED DESCRIPTION OF THE INVENTION 
The propanolamine derivatives of the present invention are compounds of 
formula 
##STR5## 
wherein R.sup.1 is hydrogen or a group of formula 
##STR6## 
n is the number 0 or 1; R.sup.2 and R.sup.5 are phenyl, 
m-trifluoromethylphenyl, thienyl or pyridyl; 
R.sup.3 or methyl; 
R.sup.4 is hydrogen, --CH.sub.2 COOH, --CH.sub.2 COO--C.sub.1-4 -alkyl, 
--(CH.sub.2).sub.2 O--C.sub.1-4 -alkyl or --(CH.sub.2).sub.2 
O(CH.sub.2).sub.1-4 --C.sub.6 H.sub.5 ; 
and a physiologically compatible salt thereof. 
The term "C.sub.1-4 -alkyl" denotes straight-chain or branched residues 
with 1-4 C-atoms such as methyl, ethyl, propyl, isopropyl, butyl and 
isobutyl. 
The term "halogen" refers to bromine, chlorine, fluorine and iodine. 
The term "m-halophenyl" refers to a phenyl group substituted with bromo-, 
chloro-, fluoro- and iodo- in the meta position. 
m-Chlorophenyl is preferred among the m-halophenyl groups R.sup.2 or 
R.sup.5, and 2-thienyl and, respectively. 2-pyridyl are preferred under 
the thienyl and pyridyl groups. 
The compounds of formula I form salts with acids, and these salts are also 
an object of the invention. Examples of such salts are salts with 
physiologically compatible mineral acids such as hydrochloric acid, 
hydrobromic acid, sulfuric acid, phosphoric acid; or with organic acids 
such as oxalic acid, methanesulfonic acid, acetic acid, propionic acid, 
citric acid, maleic acid, succinic acid, maleic acid, fumaric acid, 
phenylacetic acid or salicylic acid. Carboxylic acids of formula I can 
also be present as physiologically compatible salts. Examples of such 
salts are alkali metal, alkaline earth metal, ammonium and ethanolammonium 
salts. 
The compounds in accordance with the invention contain at least one 
asymmetric carbon atom and can accordingly be present as optically active 
enantiomers, as diastereomers or as racemates. 
Among the compounds of formula I there are preferred those in which R.sup.1 
is hydrogen, R.sup.2 is phenyl, m-halophenyl, especially m-chlorophenyl, 
or m-trifluoromethylphenylphenyl, thienyl or pyridyl, especially 2- or 
3-pyridyl, R.sup.4 is hydrogen, 2-ethoxyethyl. 2-phenethoxyethyl or 
ethoxycarbonylmethyl, especially those in which the C-atom attached to a 
methyl group R.sup.3 which may be present has the R-configuration. Those 
compounds in which R.sup.2 is phenyl or 2-thienyl and R.sup.4 is 
2-ethoxyethyl or ethoxyphenyl carbonylmethyl are especially preferred. The 
following are examples of such compounds 
(R or S)-.beta.-[[[p-(2-ethoxyethoxy)phenethyl]amino]-methyl]phenethyl 
alcohol. 
ethyl [p-[2-[[.beta.-(hydroxymethyl)phenethyl]amino]-ethyl]phenoxy]acetate, 
.beta.-[[[(R)-p-(2-ethoxyethoxy)-.alpha.-methylphenethyl]amino]methyl]phene 
thyl alcohol and 
.beta.-[[[p-(2-ethoxyethoxy)phenethyl)amino]methyl)-2-thiophenethanol. 
Further, there are preferred the compounds of formula I in which R.sup.1 
represents a group of formula (a) in which either n is the number 1 and 
R.sup.5 is phenyl or m-halophenyl, especially m-chlorophenyl, or n is the 
number 0 and R.sup.5 is phenyl, especially in which the C-atom attached to 
the group R.sub.5 has the R-configuration, R.sup.2 is phenyl or 
m-halophenyl, especially m-chlorophenyl, R.sup.3 is hydrogen and R.sup.4 
ethyl, for example. 
(RS)-m-chloro-.beta.-[p-(2-ethoxyethoxy)phenethyl][[[(R)-.beta.-hydroxyphe 
nethyl]amino]methyl]phenethyl alcohol. 
The propanolamine derivatives of the present invention can be prepared 
according to methods known in the art by 
(a) reducing an amide of the formula 
##STR7## 
wherein R.sup.1, R.sup.2 or R.sup.3 are as described above and R.sup.6 
is hydrogen, --(CH.sub.2).sub.2 O--C.sub.1-4 -alkyl or --(CH.sub.2).sub.2 
O(CH.sub.2).sub.1-4 --C.sub.6 H.sub.5, and 
(b) if desired, etherifying a phenol of formula I in which R.sup.4 is 
hydrogen to a compound of formula I in which R.sup.4 is a group --CH.sup.2 
--COOH or --CH.sup.2 COO--C.sub.1-4 -alkyl and 
(c) if desired, converting a compound of formula I into a physiologically 
compatible salt. 
The reduction according to process variant (a) can be carried out 
conveniently by means of a complex metal hydride such as lithium aluminium 
hydride (LiAlH.sub.4) in a solvent such as an ether, for example, diethyl 
ether, monoglyme, diglyme or tetrahydrofuran (THF), at a temperature up to 
the reflux temperature of the reaction mixture, preferably at room 
temperature. 
The etherification according to variant b) can be carried out with a 
compound of the formula X-R.sup.40 in which R.sup.40 is a group --CH.sup.2 
COOH or --CH.sub.2 COO--C.sub.1-4 -alkyl and X is halogen, conveniently 
iodine, or a sulfonate group, for example, methanesulfonate. The reaction 
is conveniently carried out in a solvent such as a ketone, for example, 
acetone, an ether such as THF or in dimethylformamide in the presence of a 
base such as an alkali metal hydroxide, for example, potassium hydroxide 
or sodium hydroxide, at a temperature up to the reflux temperature, 
preferably at room temperature. 
The amides of formulas II and III may be prepared according to methods 
known in the art. 
Thus, the amides II are obtained by reacting an amine of formula 
##STR8## 
with a diester of formula 
EQU R.sup.2 --CH(COOR).sub.2 V 
wherein R is C.sub.1-4 -alkyl 
Amides of formula II in which R.sup.1 is a group (a) can also be obtained 
by reacting a secondary amine of formula I in which R.sup.1 is hydrogen 
with a diester V. 
These reactions can be carried out in a solvent such as an ether, for 
example, diglyme, at temperatures up to the reflux temperature, 
conveniently at about 90.degree.-100.degree. C. 
For the preparation of the amide starting material of Example 1 
hereinafter, a solution of diethyl phenylmalonate in 50 mg of diglyme was 
treated in the manner described above with 25 g of 
p-(2-ethoxyethoxy)-phenerhylamine and stirred at 95.degree. C. for 48 hrs. 
After cooling the excess solvent was evaporated. The residue was 
chromatographed on silica gel with ethyl acetate/hexane (1:2). There was 
obtained ethyl [[[p-(2-ethoxyethoxy)-phenethyl]carbamoyl]phenyl]acetate. 
m.p. 8O.degree. C. The amide starting materials of Examples 2a), 2l) and 
2o) described infra were also obtained in crystalline form (m.p. 
108.degree. C., 94.degree.-95.degree. C. and 110.degree.-111.degree. C., 
respectively). 
The amides III are obtained by reacting an alcohol of formula 
##STR9## 
with a compound of formula 
##STR10## 
wherein Y is halogen, especially chlorine, or lower-alkoxy. 
This reaction can be carried out in the same manner as the reaction of an 
amine IV with a diester V described above. 
For the preparation of the amide starting materials III of Examples (3a) 
and (3b), 50 g of ethyl p-(2-ethoxyethoxy)phenyl acetate in 50 ml of 
diglyme were treated slowly with 25 g of (R or 
S)-.beta.-(aminomethyl)phenethyl alcohol and stirred at 95.degree. C. for 
48 hrs. The mixture was then cooled and evaporated and the residue was 
chromatographed on silica gel with ethyl acetate/hexane (1:2). 
The alcohols VI can be prepared by reducing the corresponding acids of 
formula 
##STR11## 
This reduction can be carried out analogously to the reduction of the 
amide II or III described above. 
A racemate of formula VI can be resolved readily by salt formation with an 
optically active acid such as L- or D-dibenzoyltartaric acid and is 
therefore especially suitable as an intermediate in the preparation of 
optically active compounds III and I. 
For the preparation of the alcohols VI used in Examples (3a) and (3b). 10 g 
of 3-amino-2-phenylpropanecarboxylic acid in 150 ml of monoglyme were 
stirred with 3 g of LiAlH.sub.4 for 20 hrs. Then, 12 ml of water and 3 ml 
of 10% sodium hydroxide solution were slowly added thereto. The mixture 
was filtered and the filtrate was again evaporated with toluene. There was 
obtained 8.4 g of .beta.-(aminomethyl)-phenethyl alcohol. 
For the preparation of the R- and S-enantiomers of the 
.beta.-(aminomethyl)phenethyl alcohol, the alcohol was dissolved in 200 ml 
of THF and treated with a solution of dibenzoyl-L-tartaric acid. After one 
day crystals were removed by filtration and recrystallized from ethanol 
until the rotation was constant. There was obtained (R or 
S)-.beta.-(aminomethyl)phenethyl alcohol (S.S)-2,3-di-O-benzoyltartrate. 
m.p. 172.degree.-173.degree. C., [.alpha.]D -28.4.degree. (DMSO, c=1%). 
The mother liquors were treated with a strongly basic ion exchanger, 
filtered and evaporated. The oily residue of the free amine enriched with 
the enantiomers was treated as described above, but this time with 
dibenzoyl-D-tartaric acid. There was obtained (R or 
S)-.beta.-(aminomethyl)phenethyl alcohol (R.R)-2.3-di-O-benzoyltartrate, 
m.p. 172.degree.-173.degree. C., [.alpha.].sub.D +28.2.degree. (DMSO, 
c=1%). 
The compounds IV, V, VII and VIII, insofar as they are not known, can be 
prepared according to methods known in the art, as for example, by methods 
for preparing analogous compounds IV, V. VII and VIII which are known in 
the art. Thus, the diesters V can be obtained from the corresponding 
acetic acid esters according to the methods described in Organic 
Synthesis. Collective Vol. 2, Edited by A. H. Blatt (1943) 288-289. 
EFFECT OF THE NOVEL PROPANOLAMINE DERIVATIVES 
The propanolamine derivatives in accordance with the invention can be used 
as active substances in pharmaceutical preparations for the treatment of 
obesity and/or of diabetes mellitus, especially of obese adult diabetics. 
In animal experiments an increased energy expenditure, primarily fueled by 
catabolism of body fat, has been observed upon the aministration of the 
said derivatives. Furthermore, the propanolamine derivatives in accordance 
with the invention stimulate the formation of brown adipose tissue. 
It is known that defects of the brown adipose tissue play a substantial 
role in the origin of obesity. In obese-hyperglycemic mice and in 
streptozotocin-diabetic rats these derivatives have a pronounced 
antidiabetic effect, in that they have hypoglycemic activity and reduce 
glycosuria. 
The propanolamine derivatives in accordance with the invention exhibit only 
a slight activity on the working of the heart and circulation. Moreover, 
they have only a slight activity on insulin secretion. This is of 
significance, since as is known high plasma insulin plays an important 
role in the pathogenesis of obesity. The dosage can amount to 0.5-1000 mg. 
preferably 2.200 mg, per day for an adult depending on the strength of 
activity of the individual compounds and on the individual requirements of 
the patients, whereby the dosage can be administered as a single dosage or 
in several dosages over the day. 
In addition, the propanolamine derivatives in accordance with the invention 
lead to an increase in the body protein content and a decrease in the body 
fat content. The said derivatives therefore lead to an increase in the 
lean composition of the body at the expense of fat. Accordingly, they can 
be used in human medicine for the treatment of conditions which are 
associated with high protein breakdown, for example, in convalescence 
after operations. In this case the dosages administered are the same as in 
the treatment of obesity and/or of diabetes mellitus. 
The propanolamine derivatives in accordance with the invention can also be 
used in the maintenance of meat producing animals such as beef cattle, 
pigs, sheep and poultry. As the said derivatives increase body protein 
while reducing body fat they provide a method for improving the weight 
gain and/or improving the feed utilization efficiency and/or increasing 
lean body mass. In this case the dosage forms are the same as in the case 
of vitamins. The said derivatives can also be used as feed additives in 
dosages of 0.01-100 mg/kg depending on the substance, kind of animal and 
age. 
The pharmaceutical preparations contain the active substances together with 
a compatible pharmaceutical, organic or inorganic carrier material such as 
water, gelatin, gum arabic, lactose, starch, magnesium stearate, talc, 
vegetable oils, polyalkylene glycols or white petroleum jelly such as 
Vaseline.RTM.. 
The pharmaceutical preparations are preferably administered orally, for 
example, in the form of tablets, capsules, pills, powders, granulates, 
solutions, syrups, suspensions or elixirs. The administration can, 
however, also be effected parenterally, for example, in the form of 
sterile solutions, suspensions or emulsions. The pharmaceutical 
preparations can be sterilized and may contain ingredients such as 
preserving agents, stabilizing agents, wetting agents, emulsifiers, salts 
for varying the osmotic pressure and buffer substances. 
The useful activity of the novel compounds of formula I is evident from the 
following test results: 
MATERIALS AND METHODS 
(1) -Activity on oxygen consumption 
Male albino rats weighing 160-180 g were placed in metabolic cages after 
fasting for 24 hours. The cages were ventilated with a constant 6 liter 
room air/minute which was equilibrated at a dew point of 11.degree. C. 
Samples of the spent air were collected during periods of in each case 14 
minutes after again equilibrating and the oxygen content and CO.sub.2 
content were analyzed. After an adaptation time of 4 hours the animals, 
divided into groups of 6, received either placebo (5% gum arabic) or the 
test substance (suspended in 5% gum arabic) per os. Thereafter, the 
determinations were carried out for a period of 12 hours. In Table I the 
average oxygen consumption after medication during the first 3 hours and 
the entire test duration (12 hours) is given as percentage of the oxygen 
consumption during the adaptation period. Corresponding corrections for 
changes in the placebo group have been taken into consideration. 
TABLE 1 
______________________________________ 
O.sub.2 consumption 
Compound of 
Dosage % of the value of the pre-period 
Example No. 
.mu.M/kg 1st-3rd hour 
1st-12th hour 
______________________________________ 
2a 10 149 113 
2b 3 124 107 
2c 3 132 108 
2d 3 152 127 
2j 10 137 113 
2o 10 147 115 
3a 3 152 112 
4 3 145 112 
______________________________________ 
(2) Activity on heart rate 
Male albino rats weighing 250-320 g received 6 hours after withdrawl of 
food either placebo (5% gum arabic) or the test substance (suspended in 5% 
gum arabic) per os. The animals were subsequently immobilized in 
perforated plastic tubes. The electrocardiogram was derived by means of 
bipolar subcutaneous needle electrodes. The R-peak was used to trigger a 
beat counter. The heart rate measured 1 and 3 hours after treatment was 
given in Table II as a percentage of the control value (placebo). 
TABLE II 
______________________________________ 
Heart rate 
Compound of 
Dosage (% of controls) 
Example (mg/kg) 1 hour 3 hours 
______________________________________ 
2a 30 105 100 
100 121 112 
2b 30 106 99 
100 114 105 
2c 10 103 102 
30 111 104 
2d 10 103 100 
30 111 104 
2j 100 110 -- 
2o 30 108 -- 
100 111 
3a 10 108 -- 
30 115 -- 
______________________________________ 
CONCLUSION 
The data indicate that the novel propanolamine derivatives potently 
increase energy expenditure as demonstrated by the stimulation of O.sub.2 
consumption. In contrast, the said derivatives only at high dosage exhibit 
slight activity on the working of the heart.

The following Examples illustrate the present invention but are not 
intended to limit its extent in any manner. While the examples describe 
what are at present considered to be the preferred embodiments of this 
invention, it will be obvious to those skilled in the art that various 
changes and modifications may be made therein without departing from the 
invention, and it is, therefore, aimed to cover all such changes and 
modifications as fall within the true spirit and scope of the invention. 
Unless otherwise stated, precentages and ratios relating to solvent 
mixtures are expressed in volume, purity data determined by gas 
chromatography are expressed in area %, and the remaining percentages and 
ratios are expressed in weight. Temperatures are in degrees Celsius 
(.degree. C), normal pressure is about 1 atmosphere, and room temperature 
is about 23.degree. C. Examples were carried out as written unless 
indicated otherwise. 
EXAMPLE 1 
A solution of 15 g of LiAlH.sub.4 in 600 ml of diethyl ether was treated 
while stirring with a solution of 20 g of ethyl 
[[[p-(2-ethoxyethoxy)phenethyl]carbamoyl]phenyl]-acetate. After stirring 
for 12 hours 15 ml of water and 5 ml of 10% sodium hydroxide solution were 
added to the mixture. The mixture was filtered through silica gel and the 
filtrate was evaporated. The residue was dissolved in ethanol and treated 
with the equivalent amount of oxalic acid dissolved in ethanol. After 
adding ethyl acetate there was obtained 
.beta.-[[[p-(2-ethoxyethoxy)phenethyl]amino]methyl]phenethyl alcohol 
oxalate m.p. 145.degree. C. 
EXAMPLE 2 
In a manner analogous to the methods described in Example 1 above. 
(2a) from ethyl 
[[(R)-p-(2-ethoxyethoxy)-.alpha.-methylphenethyl]carbamoyl]phenylacetate 
there was prepared 
.beta.-[[[(R)-p-(2-ethoxyethoxy)-.alpha.-methylphenethyl]amino]-methyl]-ph 
enethyl alcohol oxalate m.p. 145.degree. C. (decomposition). 
(2b) from ethyl 
[[p-(2-ethoxyethoxy)phenethyl]carbamoyl]-m-chlorophenylacetate there was 
prepared 
m-chloro-.beta.-[[[p-(2-ethoxyethoxy)phenethyl]amino]methyl]phenethyl 
alcohol oxalate m.p. 148.degree. C. 
(2c) from 
(RS)-2-phenyl-N-[(RS)-.beta.-(hydroxymethyl)phenethyl]-N-[p-(2-ethoxyethox 
y)phenethyl]ethylmalonamate there was prepared .beta., .beta.'-8 
[[p-(2-ethoxyethoxy)phenethyl]-imino]dimethylene]bis-[(RS)-phenethyl 
alcohol]hydrochloride m.p. 94.degree. C. 
(2d) from 
(RS)-2-(m-chlorophenyl)-N-[p-(2-ethoxyethoxy)phenethyl]-N-[(R)-.beta.-hydr 
oxyphenethyl]malonamate there was prepared 
(RS)-m-chloro-.beta.-[p-(2-ethoxyethoxy)phenethyl][[[(R)-.beta.-hydroxyphe 
nethyl]amino)methyl]phenethyl alcohol oxalate m.p. 130.degree. C. 
(2e) from ethyl 
(RS)-[[[(R)-.alpha.-methyl-p-(2-phenethoxy)ethoxy]phenethyl]carbamoyl]-m-c 
hlorophenyl acetate there was prepared 
(RS)-m-chloro-.beta.-[[[(R)-.alpha.-methyl-p-[2-(phenethoxy)ethoxy]pheneth 
yl]amino]methyl]phenethyl alcohol oxalate m.p. 164.degree.-166.degree. C. 
(2f) from (RS)-2-(m-chlorophenyl)-N-[(RS)-m-chloro-.beta.-(hydroxymethyl) 
phenethyl]-N-[p-(2-ethoxyethoxy)phenethyl]ethylmalonamate there was 
prepared .beta., 
.beta.'-[[[p-(2-ethoxyethoxy)phenethyl]imino]dimethylene]-bis[(RS)-m-chlor 
ophenethyl alcohol]hydrochloride m.p. 148.degree. C. 
(2g) from ethyl 
(RS)-[[[(R)-.alpha.-methyl-p-(2-ethoxyethoxy)-phenethyl]carbamoyl]-m-chlor 
ophenyl acetate there was prepared (RS)-m-chloro-.beta.-[[[(R) 
p-(2-ethoxyethoxy)-.alpha.-methyl-phenethyl]amino]methyl]phenethyl alcohol 
oxalate m.p. 145.degree. C. 
(2h) from ethyl [[p-hydroxyphenethyl]carbamoyl]phenyl acetate there was 
prepared .beta.-[[(p-hydroxyphenethyl)amino]methyl]-phenethyl alcohol 
oxalate m.p. 136.degree.-137.degree. C. 
(2i) from ethyl (RS)-[[[(R) 
.alpha.-methyl-p-(2-phenethoxy)-ethoxy]phenethyl]carbamoyl]phenyl acetate 
there was prepared 
.beta.-[[[(R)-.alpha.-methyl-p-(2-phenethoxy)ethoxy]phenethyl]amino]-methy 
l]phenethyl alcohol oxalate m.p. 165.degree.-179.degree. C. 
(2j) from ethyl [[p-(2-phenethoxy)ethoxy]phenethyl]carbamoyl]phenyl acetate 
there was prepared 
.beta.-[[[p-(2-phenethoxy)ethoxy]phenethyl]amino]methyl]phenethyl alcohol 
oxalate m.p. 145.degree. C. 
(2k) from ethyl 
[[p-(2-ethoxyethoxy)phenethyl]carbamoyl]-m-trifluoromethylphenyl acetate 
there was prepared .beta.-[[[p-(2-ethoxyethoxy) phenethyl]amino]methyl]-m 
trifluoromethylphenethyl alcohol oxalate m.p. 148.degree. C. 
(21) from ethyl 
.alpha.-[[p-(2-ethoxyethoxy)phenethyl]carbamoyl]-3-thiopheneacetate there 
was prepared 
.beta.-[[[p-(2-ethoxyethoxy)phenethyl]amino]methyl]-3-thiophene-ethanol 
oxalate m.p. 153.degree.-155.degree. C. 
(2m) from ethyl 
.alpha.-[[p-(2-ethoxyethoxy)phenethyl]-carbamoyl]-2-pyridine acetate there 
was prepared 
.beta.-[[[p-(2-ethoxyethoxy)phenethyl]amino]methyl]-2-pyridine-ethanol 
oxalate m.p. 128.degree.-129.degree. C. 
(2n) from ethyl 
.alpha.-[[p-(2-ethoxyethoxy)phenethyl]carbamoyl]-3-pyridineacetate there 
was prepared 
B-[[[p(2-ethoxyethoxy)phenethyl]amino]methyl]-3-pyridine-ethanol oxalate 
m.p. 170.degree. C. (decomposition). 
(2o) from ethyl 
.alpha.-[[p-(2-ethoxyethoxy)phenethyl]carbamoyl]-2-thiopheneacetate there 
was prepared 
.beta.-[[[p-(2-ethoxyethoxy)phenethyl]amino]methyl]-2-thiophene-ethanol 
oxalate m.p. 145.degree. C. (decomposition). 
EXAMPLE 3 
Analogously to Example 1, 
(3a) from N-[(R or 
S)-3-hydroxy-2-phenylpropyl]-p-(2-ethoxyethoxy)phenylacetamide there was 
prepared (R or 
S)-.beta.-[[[p-(2-ethoxyethoxy)phenethyl]amino]methyl]-phenethyl alcohol 
oxalate m.p. 152.degree.-154.degree. C., [.alpha.].sub.D -9.degree. (DMSO, 
c=1%) 
(3b) from the enantiomer corresponding to Example 3a) there was prepared 
the enantiomer (R or 
S)-.beta.-[[[p-(2-ethoxyethoxy)phenethyl]amino]methyl]phenethyl alcohol 
oxalate m.p. 151.degree.-154.degree. C. [.alpha.].sub.D +8 3.degree. 
(DMSO. c=1%). 
EXAMPLE 4 
3.62 g of the product of Example 2h) were stirred for 24 hours in 200 ml of 
acetone with 2.5 g of ethyl iodoacetate and 2 g of potassium hydroxide. 
The mixture was then evaporated, the residue was taken up in water and 
ethyl acetate. The organic phase was separated, dried over sodium sulfate 
and evaporated. The residue was chromatographed on silica gel. The product 
was dissolved in ethanol, treated with 1 ml of concentrated hydrochloric 
acid and evaporated with ethanol. Crystallization of the residue from 
ethanol/ ether gave ethyl 
[p-[2-[[.beta.-(hydroxymethyl)phenethyl]-amino]ethyl]phenoxy]acetate 
hydrochloride m.p. 104.degree.-105.degree. C. 
EXAMPLE 5 
An oral dosage formulation of the following composition is prepared as 
follows: 
______________________________________ 
1. Active substance of formula I, for example, 
250 mg 
(RS)-m-chloro-.beta.-[p-(2-ethoxyethoxy)- 
phenethyl][[[(R)-.beta.-hydroxyphenethyl]- 
amino]methyl]phenethyl alcohol oxalate 
2. Lactose 200 mg 
3. Maize starch 300 mg 
4. Maize starch paste 50 mg 
5. Calcium stearate 5 mg 
6. Dicalcium phosphate 45 mg 
______________________________________ 
Manufacturing Procedure 
A. Mix 1 with 2 to form mixture. 
B. Add 3-6, and mix thoroughly with mixture prepared in step A. 
C. Pass through a suitable mill and fill capsules with formulation or press 
formulation into tablet form.