SU482043A3 - The method of obtaining esters - Google Patents

Description

one

This invention relates to a process for the preparation of new compounds that can be used in medicine.

When using methods known in organic chemistry for the preparation of esters

A number of new substances with biological activity have been obtained.

The proposed method for the preparation of 5 esters of general formula 348 Y is an acidic residue of an inorganic or organic acid; may be the same or different and each means a hydrogen atom or a halogen, alkoxy, phenoxy group, a lower alkyl or trifluoromethyl group, or two of them together mean a methylenedioxy group, moreover, if the benzyl group is monosubstituted and X2 means standing in the P-position is a hydrogen atom, and 5 i 2 means a methyl group, or G d is a methyl or isopropyl group, and K, 2 is a hydrogen atom and a methyl group, then it must be straight or branched alkyl, alkenyl, cycloalkenyl or phenyl or, in case the benzoyl group is monosubstituted and Xo is ethoxy, i-butoxy, or tizobutoxy, which stands in the fl-formulation, while 1 and R 2 are in the methyl group, then 1 2 must be an alkyl, alkenyl, picloalkyl or phenyl group with a primate or a branched chain, or if the benzoyl group is monosubstituted and X2 is the primary H - butoxy group, while it is a hydrogen atom, and 2 is methylene group, then R g must mean with straight or branched chains th alkyl, alkenyl, tsiklovlkil. - either a phenyl group, or if the benzene group is disubstituted and X2 means a fluorine atom in the ft position, and Xi means an iodine atom in the m-position, X2 is a chlorine atom in the / 1-position , while Xj is a chlorine atom in the m-position and Z is an oxygen atom, and Rj 2 is a hydrogen atom, then R g must be an alkyl, alkenyl, cycloalkyl or phenyl group with a straight or branched chain, or if the benzoyl group is trisubstituted in the 3, 4, 5 position and Xj, X2, Xd are in the methoxy group, and a) F 2 and by atom vodob) R j means an ethyl group, and R is an ethyl or phenyl group and a 2-methylene group, then P must mean with a straight or branched chain) alkyl, alkenyl, cycloalkyl or phenyl group, is the amino alcohol of the general formula (-CH Z} -CH-C-CH2-OH (lIl) where Rj, R2i Chz have the indicated meanings, reacts with a reactive carboxylic acid derivative of the general formula / where X - Chd have the indicated meanings, for example with a halide , ester or anhydride, in a solvent, for example in benzene. The desired product is isolated or salified in a known manner. Salts can be, on the one hand, solimi compounds form. mules 1 prepared with inorganic acids, for example, hydrochloric, hydrobromic, sulfuric, or phosphoric acid, or with organic acids, for example, acetic, citric, tartaric, and malonic ,. AZH on the other hand, quaternary salts formed with compounds of the general formula R 4 Y I R 4 have the indicated meanings. In addition, the compound of formula I can be obtained from compounds of formula C and convert it to another or quaternary salt. If a carboxylic acid halide is used as the compound of formula IV, it is taken in an insignificant excess. / The reaction mixture is boiled for several hours. hours Example. Z-Piperidinopropyl 3 - ztorbenzoat-hydrochloride. A solution of 31.5 g of 3-piperidinopropanol in 50 ml of benzene is added dropwise with cooling to a solution of 35.5 g of 3 rt-borobenoyl chloride in 70 MP anhydrous benzene. The mixture was boiled for 3 hours under reflux, cooled, then shifted from 50 ml of ether. The crystalline 3-Chipiperidono: propyl-3-h) torbenzoate hydrochloride which is separated out is filtered off and recrystallized from a mixture of acetone and ethanol. The yield of pure product 59 g, so pl. 194.5-195.50С. Calculated,%: C 59.7; H 7.01; .N 4.64; C1 11.75 Found: C 60.00; H 7.12; N4.59; C1 10.62. 5482 Thanks to the appropriate choice of starting materials, the following compounds can also be prepared; H-piperidinopropyl-2-fluorobenzoate hydrochloride with mp. 164-166 °; 3-pilyridinopropyl-4-fluorobenzoate ™ hydrochloride with t. Pl. 194-1960; 3-morpholinopropyl-3-fluorobenzoate-hydrochloride with mp, 185–1860; 3-morpholinopropyl 3-fluorobenzoate-hydrochloride with so pl. 187-188 °; 3-morpholinopropyl 4-fluorobenzoate Hydrochloride with mp. 180 182 °; 3-morpholinopropyl 2-chlorobenzo-1-hydrochloride chloride, etc. 134-138 °; Z-morpholinogfopil-Z-chlorobenzoate-hydro, chloride with t. Pl. 164-167; 3-morpholinopropyl-4-chlorobenzoate-hydr chloride with so pl. 203-206 °; Z-morpholinopropyl-2,4-dihporbenzo tgidrokhlorid with t. Pl. 206-209 °; 2,2-dimethyl-3-morpholinopropyl-3-fluoro benzoate hydrochloride with t. Pl. 165-167 °; 2-allyl-3-morphrlinopropyl-3-fluorobenoate hydrochloride with t. Pl. 171-173 °; , 2,2,3-trimethyl-3 morpholinopropyl-3fluorobenzoate hydrochloride with m. Pl. 142-145 2-isopropyl-2-morpholinopropyl-2-fluoro benzoate hydrochloride with t. Pl. 153-155 ° C: Example 2. 3-Morfolsh-yupropil-3, 4-dimethoxybenzoate hydrochloride, A solution of 0.2 g of sodium in 10 ml of ethanol is added to 7 g of 3-morpholinopropanol and 11 methyl ether 3 , 4-dimethoxybenzoic acid. The reaction mixture is heated for 3 hours at 180 ° C, the ethanol serving as the solvent and the methanol formed are distilled off. After cooling, the reaction mixture is dissolved with dilute hydrochloric acid, clarified hot with activated charcoal, filtered, then the cooled filtrate is alkalinized with sodium hydroxide and extracted with ether. The ether solution is dried with calcined carbonate through the solution. The precipitated 3-orfolinonronyl-3, 4-dimethoxybenzoate-hydrochloride (10 g) is filtered and dried, then recrystallized from 150 ml of ethanol, mp 190-192 °, Calculated: C 55.57; H 6.99; N4.05; C1, 10.25; Found: C, 55.63; H 6.98; N4.02 C1 10.19 Due to the appropriate choice of starting materials, the following compounds can be prepared: 3-piperidinopronyl-3,4-dimeuksibenzoat-hydrochloride with t. Pl. 190-192 °; 2-isopropyl-3-piperidinopropyl-3 4.5 trimethoxybenzoate hydrochloride with so pl. 154-156 °; 3-piperidinopropyl-3,4-methylenedioxybenzoate hydrochloride with so pl. 183-184 °; 3-morpholinopropyl-3,4-methylenedioxybenzoag hydrochloride with m.p. 207-209 °; 3 m orfolinopropyl-4-tert butyl benzoate hydrochloride with t. Pl. 179-181 °; 3-phenyl-3-morpholinopropyl-3,4,5-tr and methoxybenzoate hydrochloride with m.p. 1323-morpholinopropyl-2, 4,6-trimethylbenzoate hydrochloride with so pl. 183-185; . H-piperidinopropyl-2,4,6-trimethylben-1 zoate hydrochloride with t. Pl. 165-167 °; 3-piperidinopropyl-2 methoxybenzoate hydrochloride with a melting point of 155-157 °; 3-piperidinopropyl-4-methoxybenzoate hydrochloride with m.p. 177-178 ° ;. Z-pineridinopropil-2-phenoxybenzoarhydrochloride with t .. pl. 156-157 °: 3-methyl-piperidinopropyl-3-methoxybenzoate hydrochloride with t. Pl. 158-160 °; 3-phenyl-3-piperidinopropyl-3-methoxybenzoate-hydrochloride with t; square 172-174 °; 2-methyl-3 piperidinopropyl-3-methoxybenzoate-hydrochloride with t. Pl. 168-169 °; 2,2-dimethyl-3-piperidinopropyl-3-methoxybenzoate hydrochloride with t. Pl. 154-156; 3-morpholinopropyl-2-methoxybenzoa hydrochloride with t. Pl. 123-125 °; 3-morpholinopropyl-3-methoxybenzoate hydrochloride with t. Pl. 149-151 °; Z-morpholinopropyl-4-methoxybenzoate hydrochloride with t. Pl. 172-173 °; H-morpholinopropyl-2-phenoxybenzoate hydrochloride with mp. 167-169 °; 2-isopropyl-3-pyperidinopropyl-2-phenoxybenzoate hydrochloride with so pl. 147-149 °; 3-pneridinopropyl-3-trifluoromethylbenzoate-hydrochloride with t. Nrt. 173-174 °; 2-methyl-2-ethyl-3-morpholinopropyl-2fluorobenzoate hydrochloride with m. Pl. 142-143 °; 3-morpholinopropyl-3-fluorobenzoate hydrochloride with t. Pl. 142-145 °; 3-morpholino ropi -2-methylbenzoa hydrochloride with t. Pl. 129-1300; 3-morpholinopropyl-3-methylbenzoate hydrochloride with t. Pl. 157-158 °; , 2-methyl-3-piperidinopropyl-3-methylbenzoate hydrochloride with a melting point of 142-145 °; 2-morpholinopropyl-4-methylbenzoa-hydrochloride with t. Pl. 204-205 °. PRI me R 3. 1-Benzyl-1-J - (31 fluorobenzoyl) -propyl-piperidinium chloride. Prepared according to PR1; measure 1 solution of 44 g of 3-niperidinopropyl-B-fluorobenzoate hydrochloride in 75 ml of wax is mixed with

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drop by cooling with ice with a cooled solution of 8 g of sodium hydroxide in 10 ml of water. The mixture is stirred until the crystalline substance completely disappears, then it is extracted with an equal volume of ether, and dried. The ether is distilled off by the Yu obtained 3 1 and Scheridinopropyl 3; aftorbene; l zoate, then boiled under reflux in the presence of 10 g of acetone with 7.5 g of benzyl chloride for 30 hours. Outliers

8.75 g of the quaternary salt after filtration is recrystallized from a mixture of acetone and ethanol. T. pl. 199-200 ° C.

Calculated,%: C, 67.42; H 6.94; N3.57; C1 9.05

Found,%: C 67.20; H 6.88; N3.57; C1 9.24

Thanks to the appropriate choice of starting materials, the following compounds can be obtained:

1-methyl-1-U- (2-fluorobenzoyloxy) propyl-piperidine iodide with m. Pl, 135-137 °

1-methyl-1-Y- (3-fluorobenzoyloxy) propyl-piperidinium iodide with m. Pl. 158-160 °

4-methyl-4-U- (benzoyloxy) propylmorpholinium iodide t. Pl. 159-160;

1-benzyl-1-U - (benzoyloxy) -pr6 pyliperidinium bromide with m. Pl. 198-199;

1-benzyl-1- Y- (2-fluorobenzoyloxy) propylpiperidinium chloride with mp. 171-173

PRI me R 4. 1 n- Butyl-1 - (V enZOILOX i) 1; OPTICAL VLORPHOLIJPOMID.

A mixture of 4 g of orfolipropylbenzoate prepared according to example 1 C, 8 ml of acetonitrile and 3.25 g of 1-n utilbromide are heated in a refractory tube at 90 ° C for 120 hours. After cooling, the resulting solution is mixed with acetone, and the precipitated crystals 1; n-util-1- (y-benzoyloxy) -T1-propyl-morphol-1-shibromide is recrystallized from a mixture of acetone and ether. The product yield, b g; t. 1551560C.

Calculated,%: C 55.90; H 7.30; N3.63; At 20.68

Found,%: C 56.0f; H 7.33; N3.63; At 20.73

PRI me R 5. 1 Metallil- {Y -

benzoyloxy) -tropyl morpholinium chloride.

A mixture of 8 g prepared according to example 1 of 3 - orfolinopropylbenzoate and 14 g of methyl chloride is heated in a refractory tube at 100 ° C for 200 hours. After (after cooling the precipitated 1-metal-1- (Y-benzoyloxy) -propyl-morpholinium chloride is recrystallized from a mixture of acetone

1, and ethanol.

The product yield of 7.9 g; so pl. 217-220OS.

Calculated,%: C 66.61; H 7.71; . ,12; C1 10.43

 Found,%: C 63.63; H 7.55; N4.37 :, C1 10.59

By selecting the appropriate starting materials, the following compounds can be obtained:.

1-isopropyl-1-y- (2-fluorobenzoyloxy) propyl-piperdynium dihydride with m.p. 79-81 °;

1-isopropyl-1-U - (3-fluorobenzoyloxy) propyl-piperidinium iodide C. t. Pl. 148-155 °

1-isopropyl-1-U - (benzoyloxyate) - piperidinium iodide with t. Pl. 123-124 °; : 4-isopropyl-4-U - (benzoyloxypropyl i-pyl) -Monsilolinium iodides m. Pl. 117-119 °; ;

1-metal-1-V - (benzoyloxy) -propylpiperidinium chloride with mp. 201-203 °.

Subject invention

The method of producing esters of the general formula

,

z 1-сн с-с „-о-с

 their salts of General formula 3 HI

/ - -I- II

2: | -CH-C-CH2-0-C RJYRS

where R-j - R 3 may be the same or different and is straight or branched chain hydrogen alkyl, alkenyl, cycloalkyl-- or phenyl;

C4 is a hydrogen atom, a straight or branched lower alkyl-j alkenyl-1 or benzyl group;

2 - oxygen atom or methylene; Y is the acid residue of an inorganic or organic acid;

   may be the same or different - and each means a hydrogen atom or a halogen, alkoxy, phenoxy group, a lower alkyl group, tr. c. fluoromethyl group, or two of them together mean a methylenedioxy group, and if the benzyl group is monostable and X2, which is in the fl-position-hydrogen atom, and R. 2 means by the methyl group, or F is a methyl or isopropyl group, and Rp is a hydrogen atom and methyl group, then {g must mean my or branched alkyl--, alkenyl-, cycloalkenyl or phenyl group or in the case ,. if the benzoyl group is monosubstituted and X2 is the primary n-butoxy or primary isobutoxy group in the fj position of the ethoxy, while Ri is in the methyl group, 1 C must be with a straight or J-branched chain alkyl, alkyl , cycloalkyl or phenyl group, or in the case of the benzoyl group, is m-substituted and X2 is the primary H utoxy group, while Rj and C2 are hydrogen and 2 is a methylene group, it must be a straight or developed chain; alkyl-, alkenyl-, cycloalkyl- or fe or if the benzoyl is disubstituted on the group, and X2 means the fluorine atom in the M-position, and X. denotes the iodine atom in the m-position, X2 - in the fl-position a chlorine atom, and X-, means a chlorine atom in the m-position and 2 is an oxygen atom, and R i and R 2 are at the hydrogen atom, then R h must be with a straight or branched, alkyl, alkenyl -, a cycloalkyl- or phenyl group, or if the benzoyl group is trisubstituted at the 3, 4, 5 position and Xj-Xg is in the methoxy group, and a) R j and R2 are on hydrogen atom. 482 b) Rj means an ethyl group, R 2 is an ethyl or phenyl group, and a 2-methylene group, then .3 must be straight or branched alkyl, alkenyl, cycloalkyl or phenyl. a group characterized in that the amino alcohol of the general formula / -L 2 M-CH-C-CH2-OH where R j - and Z have the indicated meanings, is reacted with a reactive carboxylic acid derivative of the general formula where they have the indicated meanings, for example halide, layered ether or anhydride, in a solvent, for example benzene, and the target product is isolated or converted into a salt or the target product is obtained from the corresponding salt in a known manner.