SU505351A3 - The method of obtaining 1- (m-acyloxyphenyl) 1-hydroxy-2-alkylaminoethanes - Google Patents

Description

(54) METHOD OF OBTAINING 1 - (lg - ACYLOXIPHENYL) - 1 - OXY - 2 - N - ALKYLYMYNYTUANO

one

 The invention relates to the way you get (n) C, not O1shahs in the literature 1 (1-a1-shloxyphenyl) -1-ox-2-M-alkylaminoethanes, which have biological activity and can be used in medicine as pharmaceuticals.

Various amino amino derivatives are known that exhibit high biological activity, for example, α-adrenergic blocking activity.

In particular, there is a known method for the preparation of 3-aral 2-alkylaminostan of the general formula A

.2 enshrined in the restoration of keto and OSHGA

where Nor R have the above values.

However, in the literature there are no data on the method of obtaining b (m-loxfesch) "ox 2-M-alkyl yinoethanes of general formula 1

IG SO-O

CH (OH) -CH2-W-a where R is tertiary butyl or cyclobutal; R, is hydrogen or an aliphatic acyl group with 1-5 carbon atoms, 25 where Y1 is alkyl with 3-19 apsham Bj is methyl or ztal, having valuable properties ha, and with ffi ms ggayy use in medvsh.

According to the invention, a method for preparing 1- {l-acyloxy-phenyl) -1-hydroxy-2-N-alkylamino-ethylates of the general formula 1 or their salts is described, which is acetyphenol of the general formula II,

It - eo

Ha

d-dHg-N,

U

in which RJ and Rj are as defined above, and P3 is hydrogen or a benzyl radical substituted if necessary.

The benzyl radical may be substituted, for example, by alkyl or alkoxy groups or a halogen atom, in particular chlorine. The reduction is carried out by catalytic hydrogenation using well-known hydrogenated hydrogen catalysts, for example Pd, Pt, Mi or complex metal hydrides with Nfeittmeii reducing force, for example, sodium borane,

If the radical Ra is a benzyl radical, then it is simultaneously removed by hydrogenolysis during catalytic hydrogenation. If the reduced ketogruths are carried out by complex metal hydrides, then the benzene group is then cleaved off by a catalytic hydrogenation group.

The starting compounds of the formula I can be obtained by acyl oxy oxyacetopheones of the formula III

o-sn2-m (

R,

wherein Ra and RS are as defined above, an acid chloride of formula IV

RS - CO - C)

in which R has the above meaning, and in the case of necessity by subsequent selective hydrogenolysis of the benzyl group.

The desired products are isolated by known methods as a base or converted into salts, using for this purpose acids such as hydrochloric, hydrobromic, hydroiodic acid, hydrofluoride, sulfuric, phosphoric, nitric, or organic; acids such as acetic, propionic, ICs, caproic, capric, valeric, fumaric, lactic, tartaric, citric, benzoic, paraoksibenzoy.na, para-aminobenzoic, phthalic, cinnamic, salicylic, ascorbic, methanesulfonic, ztansulfonova acid and 8-hlorteofillin so pl, in the form of a racemate or an optically active antipode.

P r and m units) 1. P | echlochorshd 1- (m-stearyloxyphenyl) -1-hydroxy-2-1M-ethyl-aminoethane.

A. G5 {m-stearyloxy-co-N- ztilaminoacegofenone drochloride ..

To a solution of 53.8 g (0.25 mol) of m-hydroxy-w-N-thylaminoacetophenone and HC) in 100 ml of trifluoroacetic acid, placing, at a temperature of 30 ° C, 94.5 g (0.312 mol) of stearyl chloride are added dropwise. Then the reactant mixture is kept at a temperature of 60 ° C for another 5 minutes and, if it is not cooled, is placed in 1 l of acetic ether. Crystallization of the compound occurs. The crystals are sucked off and washed with ethyl acetate.

Output 108 g (89.6% of theory); m.p. 195 ° C (after recrystallization from ethanol).

B. Hydrochloride 1- (m-steriloksifenil) -loxy-2-N-ethylaminoethash.

72 g (0.15 mol) of the compound obtained by method A in 1.44 l of methanol and 5 g of 5% palladium on the surface at 5 atm and a temperature of 60 ° C are subjected to hydrogenation. After uptake of hydrogen, the catalyst was separated and the methanol was distilled off. The crystalline residue is stirred with acetonitrile and sucked off. Yield 69 g (95.5% of theory); m.p. 113 ° C (recrystallization from ethanol).

The following compounds of formula 1 are obtained in the form of hydrochlorides in the table below.

PRI me R 5. G drochloride 1- (l "-stearyloxyphenyl) - G-hydroxy-2-N - ethylaminoethane.

And ALStearsh1oksi-zylaminoacetophenone.

22. g of m-hydroxy-ij- (N-ethyl-N-benzyl-1-xo) acetophenone hydrochloride (6.0656 mol) is dissolved in

167 ml t n. caustic soda solution, and stirring, at TeMtiepaTjpe 20 ° C, 22 g are added dropwise.

{0, mol) stearyl chloride. After expiration

Claims (2)

For 20 minutes, the acylated product is taken up in ether and then the organic phase is shaken first with 1N. caustic soda solution and then with water. The dried ethereal phase is concentrated and the residue is combined with 390 ml of 66% methanol, containing a quantity of hydrogen chloride, 10 ml of palladium chloride and 1 g of carbon under pressure, and subjected to a temperature of 60 ° C and subjected to hydrogenation. After 5 minutes, the de-benzylation is completed and the hydrogenation is completed. The catalyst is sucked off in a hot state and the desired compound is obtained from the filtrate upon cooling by crystallization. After removing the crystals, it is washed with acetonitrile. Yield 22 g (69.6% of theory); t. Sh1. 195 ° (recrystallization from ethanol). B. Hydrochloride 1 (l “-stearyloxyphenyl) - 1-OXY-2-M-ztsh1a shnoethane. Catalytic hydrogenation of 19 g (0.0395 mol) of the compound obtained in stage A in 400 ml of methanol in the presence of 0.5 g of platinum oxide at normal pressure and a temperature of 20 ° С poluchakp: 18.5 g (96.5% of theory) the final product with so pl. 113 ° (recrystallization of p of ethanol). In a similar manner, 1- (m-bu1Hryryloxyphenyl) -1-hydroxy-2-N-ethylaminoethane hydrochloride is obtained; m.p. (recrystallization from isolrpranol). PRI me R 6. Hydrochloride I- (l1-Silyloxyphenyl) -1-hydroxy-2-S-ztilaminoztana. 30.55 g (0.1 mol) of hydrochloride (Af-OKCH-a (N ethyl-M-benzylamino)) aietophore {dissolved in 250 ml of 1N sodium hydroxide solution, is reacted with 33.5 at room temperature g (0.11 mol) of stearoyl chloride to give m-stegedloxy-sh- (M-ethyl-N-benzylamino) acetophenic hydrochloride. After 20 minutes, extract with ether and shake the organic phase first with 1N sodium hydroxide solution and then water. The ether phase is dried with sodium sulfate and the solvent is distilled off. The residue is dissolved in 800 mp of methanol, neutralized with hydrochloric acid in methanol and Rene's nickel is used for hydrogenation.P1driroralium is carried out under pressure and at TeMnej, aType 40 ° C. Hydrogen uptake corresponds to 2 molar equivalents of hydrogen.After separating the catalyst, methanol is distilled off in vacuo and the desired compound is isolated from the residue. g (72.5% of theory); m.p.; 113 ° C (cross-flow steel from ethanol), Example: (l-hexylcarbonyloxy) hydrochloride-phenyl -1-hydroxy-2-N-ethylaminoethane. To a solution of 3.27 g (0.01 mol) m- (i-hexylcarbonyloxy) -a) N-ethylaminoacetophenone NS in 60 ml of methanol, stirring, at a temperature of 0-5 ° C, add 0.5 g of soda. After 5 minutes have elapsed, glacial acetic acid is adjusted to pH 5-6 and lactanol is distilled off in vacuo. The residue is dissolved in water and alkalinized with ammonium hydroxide. In addition, the base of the target compound is dissolved in ethyl acetate, dissolved over Guthree sulphate and extruded. The hydrochloride of the compound is crystallized from the residue in acetic ether and hydrochloric acid in ether. Yield 2.74 g (83.2% of theory); m.p. (recrystallization from ethyl acetate). Claim 1. Inventive method 1- (l-acyloxyphenyl I-OKCH-2-M-alkylNo-butanes of general formula CH (OH) -CHx-MH-where RI is alkyl with 3-19 carbon atoms; RI is metal or ethyl; their salts, characterized in that the acetophenone of the general formula 11 It is CO-o where RI and Rj have the above-mentioned eichexes; RZ is hydrogen yarn protecting the amniogroup {for example, substituted or unsubstituted benzyl, is subjected to reduction by one of the known methods with simultaneous or subsequent removal of the protective, and separation of the target product in a known manner in a free form dissolved in V1sche salt, as the racemate yl akpgvnogo optical antipode. 2. A method according to claim 1, characterized in that the reducing is carried out with a complex metal hydride or catalytically.