Neue Morpholinderivate und Verfahren zu ihrer Herstellung

摘要

1,160,468. Morpholine derivative. MAY & BAKER Ltd. 6 May, 1968 [8 May, 1967: 7 Nov., 1967]. Nos. 21240/67 and 50681/67. Heading C2C. Novel 2,6-dimethoxyphenyl 2-morpholinopropionate in the form of the racemate or an optically active isomer, and non-toxic acid addition salts thereof is prepared by:- (a) reacting a compound of the Formula III: where X is the acid residue of a reactive ester with morpholine. or (b) reacting a compound of the Formula IV where Z is hydrogen or an alkali metal atom: with a compound of the Formula VII: where X 1 is a halogen atom; or (c) reacting 2,6-dimethoxyphenyl 2-aminopropionate with a compound of the formula X-(CH 2 ) 2 -O-(CH 2 ) 2 -X, where X is as defined above, in the presence of concentrated sulphuric acid. Enantiomorphic forms may be obtained by resolution of the racemate, or use of optically active starting materials. ( - )-α-Bromopropionyl chloride is obtained by treating the corresponding acid with thionyl chloride and phosphorus trichloride. (Œ) - 2,6 - Dimethoxyphenyl 2 - bromopropionate is obtained by adding (Œ)-α-bromopropionyl bromide in anhydrous benzene to a solution of 2,6-dimethoxyphenol and anhydrous pyridine in anhydrous benzene and then refluxing. (-) - 2,6 - Dimethoxyphenyl 2 - bromcpropionate is prepared similarly, but using ( - )- α-bromopropionyl chloride. Pharmaceutical compositions having local anaesthetic activity and containing 2,6-dimethoxyphenyl 2-morpholinopropionate and non- toxic acid addition salts thereof are administered parenterally in association with a pharmaceutical carrier. These compositions may also contain adjuvants such as preserving, wetting, emulsifying, dispersing and solubilizing agents. They may be sterilized, e.g. by filtration through a bacteria-retaining filter, by incorporation of sterilizing agents in the composition or by irradiation.