SU470108A3 - Method for producing aminoketones - Google Patents

Description

g - 1 h II Ro-Ar-C-CH.,

- L

B

where Ar, Ri-R4 are as defined above, are treated with an amine of the general formula

five

I-l, N-Qlli-f

R.

where a Ik, Rs, and Re are as indicated above, and formaldehyde or decomposition to form formaldehyde, followed by 1, the release of target products

as base or salt, as racemate or ontic active antinode.

The reaction is usually carried out at 20-150 ° C in a solvent, e.g., a solvent, a dnoxane, glacial acetic acid.

Example 1. / -p- (1-Phenyl-1-oxypropyl 2-amino) -3-acetoxynroiiophenone.

17.8 g (0.1 mol) of 3-acetoxyacetophenone, 3 g of airaformaldehyde and 18.7 g (0.1 mol) of hydrochloride / norephedrine cues t 2 hours in 150 ml of isonropanol under reflux after 0.5 hours another 2 g of paraformaldehyde is added, cooled, the hydrochloride of the desired product is separated, and it is not rectified from methanol, i.e. 205-206 ° C.

Similarly, / - | 3- (1-phenyl1-hydroxypropyl-2-amino) -R-lropiophenones are listed, listed in the table.

Gi Rochloride precipitated with 100 ml of acetone and aerecrystallized. Before isolating the hydrochloride chloride, the solvent is distilled off.

Example 2. / -p- (1-Phenyl-1-hydroxyprocil 2 -amino) -3-y-chlorobutyryloxynopiophenone.

25.5 g (0.1 mol) of 3- (y-chlorobutyryloxy) acetophenop, 6 g of paraformaldehyde, 18.7 g (0.1 mol) of hydrochloride / norephedrine, 100 ml of isopropanol and two drops of glacial acetic acid are heated 3 under reflux, after 1 hour another 6 g of paraformaldehyde is added, the solvent is distilled off, the precipitate is treated with ether and immediately with water, and the hydrochloride is non-recrystallized from a mixture of pzopropanol-methanol, m.p. 181-182 ° C.

Example 3. / -p- (1-phenyl-1-hydroxypropyl 1 -amino - 4- (y-chlorobutyrylox) -propiopheno,

 From 24.5 g of (y-chlorobutyryloxy) acetophenone, 3X6 g of paraformaldehyde, 18.7 g of hydrochloride / norephedrine, and 100 ml of isoiropanol with two drops of glacial acetic acid

as in example 2, after recrystallization from isopropanol receive the hydrochloride of the target product, so pl. 175-176 ° C.

Example 4. / - | 3- (l-phenyl-l-oxyppropyl 2-amino) -l-acetoxypropio-naphthon-2.

Starting from 33 g (0.145 mol) of 1-acetoxy-acetonaphthon-2, 4.5 + 4.5 g of paraformaldehyde, 27 g (0.145 mol) of hydrochloride / α-norephedrine and 100 ml of isopropanol, similarly to irimer 1, the hydrochloride of the desired product is precipitated with acetone and recrystallized from isopropanol, t. pl. 177-178 ° C.

Example 5. / -r- (1-Phenyl-1-hydroxyprpyl 2 -a.mino) -4-acetoxypropionaphton-1.

From 36 g (0.158 mol) of 4-acetoxy-acetonaphthone-1, 4.5 + 4.5 g of paraformaldehyde and 29.4 g (0.158 mol) of hydrochloride / α-norephedrine in 100 ml of isopropanol, as in Example 1, receive the hydrochloride of the desired product, which is precipitated with acetone and recrystallization — a mixture of ethanol, t. pl. 191 - 192 ° C.

Example 6. o, / - | 3- 1- (4-hydroxyphenyl) -1-hydroxypropyl-2-amino-3- (p, p - dimethylacryloylamino) -propiophenone.

52 g (0.24 mol) of 3- (p, | 3-dimethylacryloylamino) acetophenone, 7.8 g of paraformaldehyde, and 40.6 g (0.2 mol) of d, l-4-oKCH norephedrine hydrochloride in 200 ml of bale isopropanol 2 hours under reflux, 100 ml of isopropanol are distilled off, 100 ml of acetone are added to the residue, the precipitate is stirred with 200 ml of water, it is filtered off with suction, washed with the acetone hydrochloride of the desired product and recrystallized from methanol, m.p. 200 ° C.

Example 7. / - | 3- (1-Phenyl-1-hydroxypropyl 2-amino) -3- (P, p - dimethylacryloylamino) propiophenone.

21.7 g (0.1 mol) of 3- (p, p-dimethyl-acrylonamino) -acetophenone, 3.9 g of paraformaldehyde and 18.7 g of hydrochloride / -Noref) edrin in 100 ml of isopropanol are boiled under reflux for 6 hours, cooled, stirred with ether and recrystallized from isopropanol, so pl. hydrochloride of the target product 164 ° C.

Example 8. / -p- (1-Phenyl-1-hydroxyproyl 2 -amino) - 4- (p, p - dimethylacryloylamino) propiophenone.

Using 4- (p, p-dimethylacryloyl) acetophenone and 120 ml of isopropanol, as in Example 7, the hydrochloride of the desired product is obtained, which is recrystallized from methanol, mp. 217-218 ° C.

Example 9. th, / - | 3- 1- (4-Hydroxyphenyl) -1-ox-1-2-amino-4 - (P, p - dimethylacryloylamino) -propiophenone.

Using 21.7 g (0.1 mol) of 4- (p, 6-dimethylacryloylamino) -acetophenone, 3.9 g of paraformaldehyde, 20.3 g (0.1 mol) of hydrochloride, / - 4-oxynorephedrine and 150 ml of isopropanol as in example 6, receive the hydrochloride of the target product, so pl. 210-211 ° C.

Example 10. / - | 3- (1-Phenyl-1-hydroxypropyl 2-amino) -2 - (p, p - dimethylacryloylamino) propiophenone.

16 g (0.074 mol) of 2- (p, B-Dimethylacryloylamino) -acetophenone, 2.9 g of paraformaldehyde and 13.8 g (0.074 mol) of hydrochloride / -norephedrine in 50 ml of isopropanol are heated for 6 hours with a reflux condenser, cooled, mixed with ether, recrystallized from methanol and the hydrochloride of the final product is recovered, m.p.

Example 11. th (, / - | 3- 1- (4-hydroxyphenyl) -1-hydroxy1-propyl-2-amino-4-carboxetiaminopropiophenone.

62.1 g (0.3 mol) of 4-carbethoxyaminoacetophenone, 11.7 g of paraformaldehyde and 60.9 g (0.3 mol) of hydrochloride,; - 4-oxinorephedrine in 300 ml of isopropanol is heated for 3 hours under reflux, cooled , recrystallized from methanol and obtain 19 g of the hydrochloride of the crude product, so pl. W8 ° C.

Example 12. (4-hydroxyphenyl) -1-hydroxypropyl-2-amino-3-acetoxypropiophenone.

17.8 g (0.1 mol) of 3-acetoxyadetofenone, 4 g of airaformaldehyde and 20.3 g (0.1 mol) of hydrochloride with, / - 4-hydroxyorophedrine in 150 ml of isopropanol are boiled for 4 hours under reflux, and after 2 hours, 2 g of paraformaldehyde are additionally introduced, the solvent is distilled off, the residue is shaken with water and ether, the oily substance is dissolved in isopropanol, precipitated with ether and

hydrochloride is recrystallized from ethanol, t. Il. 173-174 ° C.

Example 13. 3-p- (1-Phenyl-1-hydroxypropyl 2-amino) -3- (pp-dimethylacryloyloxy) proliofenone.

21.8 g (0.1 mol) of 3- (p, p-dimethylacryloxy) -acetophenone, 3 g of araformaldehyde and 18.7 g of hydrochloride / -norephedrine in 100 ml of czopropanol are boiled for 3 hours with a reflux condenser, and after 1 hour additionally

1.5 g of paraformaldehyde are introduced, oh, the resulting hydrochloride is extracted from ethanol and recrystallized; t. Il. 189-190 ° C.

Example 14. o, (4-hydroxyphenyl) -1-hydroxypropyl-2-amino-3- (p, p-dimethylacryloyloxy) propiophenone.

21.8 g of 3 - (| 5.6 - dnmethylacryloyloxy) acetophenone, 3 g of paraformaldehyde and 20.5 g of hydrochloride with, / - 4-oxinorephedrine in 100 ml of isonor01 aiol are boiled for 3 hours with a reversible refrigerator, and after 1 hour of addition, 1.5 g of paraformaldehyde are added, the solvent is distilled off, the residue is shaken with water and ether, the oily product is recrystallized after solidification

pz isoiropanol and isolate the hydrochloride of the desired product, m.p. 173-174 ° C.

Example 15. p- (1-Phenyl-1-hydroxyethyl-2 amino) -3- (p, p-dimethylacryloylamino) propiophenone.

24 g (0.11 mol) of 3- (p, p-dimethylacrploylamino) -acetophenone, 17.4 g (0.1 mol) of 1-pheny hydrochloride, t-1-hydroxyethyl-2-amine and 3.6 g of aira formaldehyde in 70 ml of isopropano, la boil for 7 hours under reflux, cool with ice and treat with aqueous ammonia, dilute with water, extract with ether, dry the extract, mix it with gasoline and crystallize the base,

in the processing of which with an ethanolic solution of fumaric acid io, 1 is fumarate, so pl. f74 ° C.

Example 16. (/ g-Chlorophenyl) -1-oxypropyl-2-amino-3- (ppdimethylacrylloylamino) -propnophenone.

22 g (0.1 mol) of 3- (p, p-dimethylacryloylamino) -acetophenone, 21 g (0.1 mol) of hydrochloride / g-chloroephedrine and 3.9 g of paraformaldehyde in 70 ml of isopropanol are boiled for 6 hours with reverse cooler, cooled with ice and treated with an aqueous solution of ammonia, the free base is separated, recrystallized from ether, and the hydrochloride is precipitated from ethanol-ether, m.p. 156-158 ° C. Example 17. (p-Fluorophenyl) -1-hydroxyprop l - 2-amino-3 - (pp-dimethylacryloyl) -propnophenone. 18 g (0.09 mol) of 1 - ("- fluorophenyl) -1-hydroxypropyl-2 -amino hydrochloride, 22 g (0.1 mol) of 3- (p, p-dimethylacryloylmio) -acetophenone and 3.6 g of paraformaldehyde 70 ml of isopropanol are boiled under reflux for 6 hours, the solvent is distilled off, the residue is dissolved in 300 ml of acetone, the hydrochloride is recrystallized, which is purified through a base and then recrystallized from an-lanol-ether mixture, m.p. 166 ° C. Example 18. | 3-G1 - (/ g-Methylphenyl) -1-hydroxyroyl - 2 -amino -3- (p, (: J-dimethylacryloyl)) proiophenol. 20.5 g (0.1 mol) of hydrochloride d- Methyl Norepredria, 22 g (0.1 mol) of 3- (I | 3, p-dimethyl-acryloyl miio) acetopheion, 3.9 g (0.13 mol) of paraformaldehyde and 70 ml of isopropanol c 6 hours with reflux condenser, distilled solvent, dissolve the residue in 300 ml of acetoia, with ice cooling, treat with aqueous ammonia solution, crystallize free base from ether, treat with isopropanol solution of hydrogen chloride and precipitate hydrochloride with acetone mp 136 ° C Example 19 (d-Methylphenyl) -oxybutyl-2-amino-3- (p, p-dimethylacryloylamino) iroiophenone 24 g (0.11 mol) 3 - ((3, p-dimethylacryloylamino) acetophenone, 21.5 g (0.1 mol) of 1- (l-methylfeiyl) -1-hydroxybutyl-2 amine hydrochloride, 3.6- | - 1.5 g of naraformaldehyde in 70 ml of isoironanol are heated 6 for one hour at RP 5 under reflux, the solvent is distilled off, the residue is dissolved in acetone, internal, the compound lasts, which is non-recrystallized twice from methanol-acetone, so on. 184-186 ° C. Prnmer 20. / -p- (1-Phenyl-1-hydroxypronyl 2-amino) - 3- (aminocinnamic acid) -propiophenoia. 19.3 g of hydrochloride (-p - (- feiil-1-oxnropyl-2-amino) -3-amino iropiophenone are dissolved in 120 ml of dimethylformamide, 4.1 ml of sodium chloride are added, mixed at room temperature with a solution of 9.8 g cinnamic acid chloride in 25 ml of acetoia, after 15 min, treated with 300 ml of 3% hydrochloric acid and the hydrochloride is recrystallized from metapol, so pl. 122--127 ° C. Example 21. / -p- (1-Phenyl-1-hydroxyroyl 2 -amipo) -3- (4 - metroplasmicoric acid) propiopheion. To a solution of 16.7 g of hydrochloride / -p- (1-phenyl-1-hydroxypropyl-2-amipo) -3-aminopropiophenone in 120 ml of dimethylformamide is added 4 ml of pyridium, mixed at room temperature with 9 g of methylcinnamic acid chloride, dissolved 300 ml of 3% hydrochloric acid are added in 15 ml of acetone in 15 ml, and the hydrochloride of the desired product is recrystallized from ethanol and a few drops of isopropyiol-hydrochloric acid, m.p. 144 ° C. Example 22. (i, (4-hydroxyphenyl) -1-hydroxypropyl-2-a "o - 3- (4-methylaminocoric acid) -propiophenone. 17.5 g of hydrochloride ((, (4-hydroxyphenyl) 1 -O1 syprrpyl 2-amino-3-amionopiophenoia is dissolved in 120 ml of dimethylformamide, 1 pyridine is added, mixed at room temperature with 4-chloride of methylcinnamic acid dissolved in 25 ml of acetone, after 16 min it is treated as in Example 21, instead of using ethanol isopropanol, and the hydrochloride is isolated, mp 166-167 ° C. Example 23. a, (4-Oxypheyl) -1-oxy-pyr-2 -amino-3- (aminocinnamic acid: utah) -propiophenone. 17.5 g gi rochloride d, l-fi-l- (4-oxyphenyl) -1-hydroxypropyl-2-amino-3-amino iropiophenone in 120 ml of dimethylformamide, 4 ml of pyridine and a solution of 8.3 g of cinnamic acid chloride in 25 ml of acetone in analogy to example 21, the hydrochloride is obtained the target product, which is dissolved in ethanol, is planted with water and dried for 3 hours at 70 ° C, mp 147-148 ° C. Example 24. (4-hydroxyphenyl) -1-oxypropyl-2-ampoule 3- (4-chloramnnokorichpa acid) -iropiofeion. As in Example 23, by replacing cinnamic chloride with 10.5 g of 4-chloride of chlorocinnamic acid, the desired product is obtained, from which a similar irimer 22 is synthesized and the hydrochloride is extracted, m.p. 160-162 ° C. Example 25: f-(1-Phenyl-1-oxypropyl 2-amino) -3 - (4-chloraminocoric acid) -propiophenone. As in Example 22, from 16.7 g of hydrochloride / -r- (1-phenyl-1-hydroxypropyl-2-amino) -3-amino iropiophenone, dissolved in 120 ml of dimethylformamide, 4 ml of pyridine and a solution of 4-chloride chlorocaric acid in 25 ml of acetone recovered the desired product hydrochloride, m.p. 106 ° C (decomp.). Example 26 / -p- (1-Phenyl-1-hydroxypropyl 2 -amipo) -3 - (2 - chloraminocinnamic acid) -propiophenone. From a solution of hydrochloride 16.7 g / -p- (1-phenyl-1-hydroxypropyl-2-amino) -3-aminopropiophene in 120 ml of dimethylformamide, 4 ml of pyridium and a solution of 2-chloride of chlorocinnamic acid in 25 ml of acetone as in Example 22 get the hydrochloride of the target product, so pl. 142-146 ° C (decomp.). Example 27 (, (4-Hydroxyphenyl) -1-oxynroyl-2-amino-3- (2-chloraminocinnamic acid) proprophenone. To a solution of 17.5 g of (4-oxyphenyl) -1-hydroxypropyl-2-amino-hydrochloride 3-amipopropiofepone in 120 ml of dimethylformamide is added with 4 ml of pyridine and a solution of 2-chloro chlorocinnamic acid in 25 ml of acetone and, as in Example 22, the hydrochloride of the left product, m.p., 168-170 ° C.

Example 28. / -p- (1-Phenyl-1-hydroxypropyl 2-amnno) -3 - (3-methoxy-aminocinnamic acid; 1 mo) -propiophenone.

A solution of 16J g of hydrochloride / -r- (1-phenyl-1oxypropyl-2-amino) -3-aminopropiophenop in 120 ml of dimethylformamide and 4 ml of pyridine is mixed at room temperature with a solution of 9.8 g of methoxycinnamic 3-chloride in 25 ml of acetone and analogously to example 22 crystallisot hydrochloride of the target product, after pre-treatment of the solution with ether, so pl. 172-175 ° C.

Example 29. s /, / - | 3- 1-4- (Hydroxyphenyl) -1-oxypropyl-2-amio-3 - (3-methoxyaminocinnamic acid) -propiophenone.

From 17.5 g of hydrochloride, (4-hydroxyphenyl) -oxypropyl-2-amino-3-aminopropiophenone, dissolved in 120 ml of dimethylformamide, 4 ml of pyridine and a solution of 3-chloromed methoxycinnamic acid in 25 ml of acetone, as in Example 28 , get the hydrochloride of the target product, so pl. 193-195 ° C.

Example 30. S, (4-hydroxyphenyl) -1-hydroxy-propyl-2-amino-3 - (a-methylaminocinnamic acid) -propiophenone.

A solution of 17.5 g of rf hydrochloride, (4-Oxyphenyl) -1-oxipropyl-2-amino-3-aminopropiophenone in 120 ml of dimethylformamide and 4 ml of pyridine is mixed at room temperature with a solution of 9 g of methylcinnamic acid a-25 ml. 25 ml acetone, after 15 minutes, as in Example 22, the hydrochloride of the desired product was isolated, m.p. 178-180 ° C.

Example 31, / - p- (1-Phenyl-1-hydroxypropyl 2-amipo) -3- (4-methoxyaminocinnamic acid) -P1) oglyopheno.

From 16.7 g of d, hydrochloride, / - p- (1-phenyl-1-hydroxypropyl - 2-amino) -3 - aminopropiophenop, dissolved in 120 ml of dimethylformamide, 4 ml of pyridine and a solution of 9.8 g of 4-chloride methoxycinnamic acid 25 ml of acetone analogously to example 22 receive the hydrochloride of the target product, so pl. 178-180 ° C.

Example 32. s, / - | 3- 1- (4-aq1 Ciphenyl) -1-oxinropyl-2-amino - 3- (4-methoxy-aminocoric acid) -propiophenone.

Using 17.5 g of hydrochloride s, / - | 3- 1- (4-Oxyphenyl) -1-hydroxypropyl-2-amino-3-amia-o-propiocenoenia, dissolved in 120 ml of dimethylformamide, 4 ml of pyridine and a solution of 9.8 g of 4-chloride methoxycritic acids in 25 ml of acetone, as in Example 28, after a few hours, the hydrochloride of the desired product is obtained to the dis, t. Il. G83--184 ° C.

Example 33. p- (1-Phenyl-1-hydroxyethyl-2 lipo) -3 - ((1p - dimethylaminoacrylic acid) -ropiofepon.

24 g (0.11 mol) of 3- {p, p-dimethylaminoacrylic acid) -acetophenone, 17.4 g (0.1 mol) of 1-phenyl-1-hydroxyethyl-2-amine hydrochloride and 3.6 g of paraformaldehyde in 70 ml of isopropane .la 11a1 are boiled under reflux for 7 hours, while cooling with ice, an aqueous solution of ammonia is added, diluted with water, the base is treated with ether, dried

the ether phase is mixed with benzino.m, the base is crystallized out by adding: from the ethanolic solution of fumaric acid, and fumarate is obtained, i.e. 174 ° C.

5 Example 34. (7g-Chlorophenpl) -1-hydroxypropyl-2-amino - 3- (p, p - dimethyl-amino-acrylic acid) -propiophenol.

22 g (0.1 mol) of 3- (p, p-dimethylaminoacrylic acid) -acetophenone, 21 g (0.1 mol)

0 chloronephedrine hydrochloride and 3.9 g (0.13 mol) of paraformaldehyde in 70 ml of isopropanol are boiled for 6 hours under reflux, while cooling with ice, treated with an aqueous solution of ammonia, the oxygen is recrystallized from ether to obtain the hydrochloride from ethanol Efio, t. pl. 156-158 ° C.

Example 35. (71-Fluorophenyl) -1-hydroxypropyl-2-amino-3 - (p, p - dimethylaminoacrylic acid) -propiophenone.

18 g (0.09 mol) of 1 - (;; g-fluorophenyl) -1-hydroxypropyl-2 -amine hydrochloride, 22 g (0.1 mol) of 3- (p, p-dimethylaminoacrylic acid) -acetophenone and 3.6 g paraformaldehyde in 70 ml

5 isopropanol is heated under reflux for 6 hours, evaporated, the residue is dissolved in 300 ml of acetone, crystallized hydrochloride, fed through a base, and recrystallized from ethano-t-ether, t. Il.

0 165 ° C.

Example 36. (p-Methylphenyl) -1-hydroxypropyl-2-amino-3-(p, p-dimethylaminoacrylic acid) -cropiophenone.

20.6g (0.1 mol) of p-methylior5 ephedrine hydrochloride, 22 g (0.1 mol) of 3- (pp-dimethylaminoacrylic acid) -acetophenone, 8.9 g (0.13 mol) of paraformalGdeg and n 70 ml of isopropanol pagret 6 hours under reflux, evaporate, dissolve the residue in

0 300 ml of acetone, extract the base, treat with an aqueous ammonia solution and cool with ice, crystallize it from ether, add acetone and a mixture of isopropanol-hydrochloric acid and precipitate the hydrochloride, t, pl.

five .

Example 37. (p-Methylpheipl) -1-hydroxybutyl-2-amio-3- (p, p-dimethyl-iiokopropyl acid) -propiophepopop. 24 g (0.11 mol) of 3- (p, p-dimethylphenoic acid) -ai, stofenone, 21.5 g (Oh, mol) of 1 - ("-methylphenyl) -1 -oxybutyl 2 -amine hydrochloride and 3.6 g + 1.5 g of paraformaldehyde in 70 ml of isonronanol at pH 5 is heated for 6 hours under reflux, pack up,

5 dissolve the residue in acetone, crystallize

compound and twice recrystallized

ggo from methanol - ai..concrete, t. p. 184-

186 ° C.

Example 38. -P- (1-Phenyl-1-oxypropyl | 2-amino) -3-fepoxycarbonylaminpropane-phenophenone.

16.7g of hydrochloride (-p- (1-phenyl-1-oxynroyl-2-amino) -3-aminopropiophenone are dissolved in 120 ml of dimethylformamide, 5 ml of pyridine are added and mixed at room 11

After heating with a solution of 7.8 g of phenyl ester of chloroformic acid in 25 ml of acetone, 300 ml of 3% hydrochloric acid are added after 15 min, the hydrochloride is crystallized and one hundred is recrystallized from ethanol, m.p. 178-180 ° C.

Example 39. th, (4-hydroxyphenyl) -1-hydroxypropyl-2-amino-3-phenoxycarbonyamyopropiophenoi.

To a solution of 17.5 g of d, (4oxyphenyl) -1-0Xypropyl-2 -amio-3-aminopropiophenone hydrochloride in 120 ml of dimethylformamide, 4 ml of pyridine are added, mixed at room temperature with 7.8 g of phenyl ester of chloroformic acid, dissolved in 25 ml of acetone, and, as in example 38, extract hydrochloride, so pl. 196-197 ° C.

Example 40. -P- (1-Phenyl-1-oxinronyl 21-amino) -3 - (a-methylaminocinnamic acid) -propiophenone.

From 16.7 g of hydrochloride / -p- (1-phenyl-1-hydroxypropnl-2-amino) -3-amino-iropiophenone, dissolved in 120 ml of dimethylformamide, 4 ml of pyridine n solution of 9 g of methylcornic acid chloride in 25 ml of acetone Analogously to Example 22, the desired product hydrochloride was isolated, m.p. 168-169 ° C.

The subject of the invention. A method for the preparation of total formula amino ketones.

and K4

Ri4 II I

R 2 -Ag-C-CH-CH-Sh-Gi.-. .

where Ar is phenyl or naphthyl; alk is branched or unbranched, saturated or unsaturated C-Se-alkylene, which may be substituted with a halogen, hydroxy, alkoxy or acyloxy group;

RI is an acnloxy, acyloxyalkoxy, acnlamino or acylalkylamino group in which the acyl can be a residue of a complex phenyl hemiether of carbonic acid or saturated or unsaturated, branched or unbranched Cz-Xyu-fatty acids, substituted to a lesser extent

12

for one phenyl, with at least one phenyl substitutions1, ene for Ci-Се-alkyl and / or Ci-Сб-alkoxygroup, and / or hydroxy group, and / or halo;

R4 is hydrogen or lower alkyl;

R, RS, RS and Re are the same or different, hydrogen, halogen, hydroxy, lower alkoxy, acyloxy, amino, alkylamino, dialkylamino, acylamino, nitro, lower alkyl, lower haloalkyl or lower alkylthiolgne, and The acyl can be a residue of saturated or unsaturated, branched or unbranched, unsubstituted or substituted by halogen, hydroxy, acyloxy, keto, lower alkoxy or phenyl C2-Syu-fatty acids, benzoic acids, which can be mono- or polysubstituted with a halo, oxy, acyloxy, lower alkyl whether lower alkoksigrunnu NLP lower aliphatic carbonic acid half esters, or residue of carbonic acid semiester phenyl or a saturated or unsaturated, branched or unbranched C -oo-fatty acids, sr-substituted by at least one mensche fepil. wherein at least one phenyl is substituted with, a galkyl and / or C | -Se-alkoxy group, and / or a hydroxy group, and / or a halo, or their salts, characterized in that, a ketone of the general formula

Po r,

|; h II I

RzjAr-C-CH ,,

fiX where Ar, RI-R4 - as indicated above, is treated with an amine of the general formula

- „w

H, N

where alk, Rs and Re are as defined above, and formaldehyde or a substance capable of decomposing to form formaldehyde, followed by isolation of the desired product as a base or salt, as a racemate or an optically active antipode.