Alfa Chemicals Italiana S.p.a.

Alfa Wassermann S.p.a.

Presidenza Del Consiglio Del Ministri-ufficio Del Ministro Per Il

Ministero Dell'universita E Delle Ricerca Scientifica E Tecnologica

Giancarlo Tamerlani

Vincenzo Cannata

Graziano Zagnoni

Mauro Morotti

Claudio Calzolari

Naphthalenes of formula ##STR1## wherein X represents COCH.sub.3, COC.sub.2 H.sub.5, CH(CH.sub.3)COOH, CH(CH.sub.3)COOR, CH(CH.sub.3)CN and CH(CH.sub.3)CONHR.sub.1, R represents alkyl and R.sub.1 represents hydrogen, alkyl or hydroxyalkyl, are debrominated by means of acceptors of bromine, like alkylarenes and alkoxyarenes, in the presence of Lewis acids.

Process for the debromination of

New process for the synthesis of the .alpha.-(1-m.ethylethyl)-3,4-dimethoxyacetonitrile of formula (I): ##STR1## which is known as an intermediate in the synthesis of the drug internationally known as verapamil. The process starts from the isobutyryl-3,4-dimethoxybenzene of formula (II): ##STR2## which, by means of the Darzens condensation, gives an epoxyester which, by alkaline hydrolysis and subsequent decarboxylation, gives the .alpha.-(1-methylethyl)-3,4-dimethoxybenzeneacetaldehyde. This product is reacted with hydroxylamine to obtain the corresponding oxime that, by dehydration, gives the nitrile of formula I.

Process for the synthesis of the

New process for the synthesis of the N-methyl-3,4-dimetoxyphenylethylamine of formula ##STR1## intermediate in the synthesis of the drug internationally known as verapamil. The process starts from the 3,4-dimethoxybenzaldehyde which, by means of a Darzens condensation, gives an epoxyester that, by alkaline hydrolysis and subsequent decarboxylation, gives the 3,4-dimethoxyphenylacetaldehyde. This aldehyde gives the amine of formula I by reaction with monomethylamine followed by reduction with sodium borohydride.

Process for the synthesis of the N-methyl-3,4-dimethoxyphenylethylamine

New process for the synthesis of optically active aminoacids of formula ##STR1## by treating compounds of formula ##STR2## which an optically active alcohol of formula

Process for the synthesis of optically active aminoacids

New process for the synthesis of the levodopa, L-(-)-2-amino-3-(3,4-dihydyphenyl)propionic acid, drug used in the treatment of the Parkinson's disease. The process consists in resolving with d-camphorsulfonic acid, or with a salt thereof, the d,l-2-amino-3-(3,4-dimethoxyphenyl)propionitrile, obtained from the 3,4-dimethoxyphenylacetaldehyde, and in the subsequent hydrolysis and demethylation, by means of concentrated solutions of haloid acids, of the d-2-amino-3-(3,4-dimethoxyphenyl)propionitrile and of salts thereof.

Process for the synthesis of the levodopa

A new process for the optical resolution of racemic mixtures of .alpha.-naphthylpropionic acids of formula ##STR1## wherein R.sub.1 is (C.sub.1-6) alkyl and R.sub.2 represents hydrogen or a halogen atom comprises reacting a racemic mixture of a compound of formula II ##STR2## wherein R.sub.1 and R.sub.2 have the above seen meanings and R.sub.3 is a reactive group, with an optically active aminoacid of formula ##STR3## wherein R.sub.4 represents a (C.sub.1-8) alkyl, phenyl, substituted phenyl, benzyl, substituted benzyl or carboxy, and m is an integer from 0 to 4, to give a pair of diastereoisomeric amides of formula ##STR4## wherein R.sub.1, R.sub.2, R.sub.4 and m have the above seen meanings, and M is a hydrogen atom or a cation of an alkali metal or a cation of an organic base. Compounds IV are resolved into the single diastereoisomeric amides d,d or 1,d, or d,1 or 1,1. Acid hydrolysis gives the optically active compound I.

Optical resolution of racemic mixtures of alpha-naphthylpropionic acids

A new process for the optical resolution of racemic mixtures of .alpha.-naphthyl-propionic acids of formula ##STR1## This process comprises reacting a racemic mixture of a compound of formula ##STR2## with an optically active substance of formula R.sub.4 --NH.sub.2 (III), said substance being a .beta.-aminoalcohol, thus forming a pair of diastereoisomeric amides which are resolved into the single diastereoisomers by fractional crystallization. The obtained single diastereoisomeric amide is then hydrolyzed to give the desired optically active .alpha.-naphthyl-propionic acid of formula ##STR3## In the above compound I.fwdarw.III and VI, R.sub.1 is (C.sub.1-6)alkyl, R.sub.2 stands for hydrogen, halogen, mercapto, (C.sub.1-6)alkylthio, phenylthio, benzylthio, (C.sub.1-6)alkylsulfonyl, benzenesulfonyl, benzenesulfonyl substituted by halogen or (C.sub.1-4)alkyl, R.sub.3 is a reactive group and R.sub.4 is the residue of a primary or secondary alcohol.

Process for the optical resolution of racemic mixtures of

A process for the optical resolution of racemic mixtures of .alpha.-naphthyl-propionic acids of formula I ##STR1## which consists of reacting a racemic mixture of a compound of formula II ##STR2## with an optically active compound of formula III

A new process for the preparation of the d-2-(6-methoxy-2-naphthyl)-propionic acid of formula ##STR1## which comprises resolving a racemic mixture of the d- and 1-2-(5-halo-6-methoxy-2-naphthyl)-propionic acids of formula ##STR2## wherein halo stands for a halogen atom, recovering the d-isomer and subjecting this isomer to catalytic dehalogenation. Compound I is obtained in very high yields and with a high purity degree.

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Pontecchio Marconi, Italy

Giancarlo Tamerlani