Patent GB-1274262-A (GB)
Title: Dibenzocycloheptene derivatives
IPC: C07C13/547
Filed: 1969-05-01
Abstract: 1,274,262. 1,5-Disubstituted-dibenzocycloheptene derivatives. F. HOFFMANN-LA ROCHE & CO. A.G. 1 May, 1969 [3 May, 1968], No. 28705/71. Divided out of 1,274,261. Heading C2C. Novel compounds of Formula Ia and Formula Ib wherein R 1  is H or methyl and R<SP>1</SP> is methyl or an acetyl group ketalized by a C 1-7  alkanol or glycol and N-oxides of compounds where R 1  is methyl, are prepared by one of the following methods:- When a compound of Formula Ia in which R 1  represents a methyl group is to be prepared, a corresponding 5H - dibenzo[a,d]cyclohepten-5- one or 10,11 - dihydro - 5H - dibenzo[a,d]cyclohepten-5-one is reacted directly, for example, with 3-dimethylaminopropyl magnesium chloride and the reaction product is subsequently hydrolysed. When a compound of Formula Ia in which R 1  represents a hydrogen atom is to be prepared, it is recommended to use N-methyl- N-benzyl-aminopropyl magnesium chloride as the reagent for the reaction. After completion of the reaction and subsequent hydrolysis, the resulting product is reacted with chloroformic acid ethyl ester and the resulting 5-hydroxy-5- [3 - (N - methyl - N - carbethoxy - amino) - propyl] compound is subsequently hydrolysed, spontaneous decarboxylation occurring with the formation of the corresponding 5-hydroxy-5- (3-methylaminopropyl) compound. Compounds of Formula Ib are obtained, for example, by reacting an appropriate 5H- dibenzo[a,d]cyclohepten-5-one or 10,11-dihydro- 5H - dibenzo[a,d]cyclohepten-5-one with ethyl magnesium bromide and hydrolysing the reaction product. The resulting 5-hydroxy-5-ethyl compound is dehydrated with acetyl chloride and subsequently treated with formic acid and hydrogen peroxide. There results a 5-hydroxy-5- (1-hydroxy-ethyl) compound which is dehydrated with aqueous sulphuric acid to the corresponding 5-acetyl compound. By treatment with formaldehyde and methyl- or dimethylamine hydrochloride there is obtained a 5-(methyl- or dimethylaminopropionyl) compound which, after reduction with sodium borohydride is converted into the corresponding compound of Formula Ib. The compounds of Formulµ Ia and Ib in which R 1  represents a methyl group can be converted by oxidation into the corresponding N-oxides. The oxidation can be carried out, for example, by treatment with hydrogen peroxide in a solvent such as, for example, methanol or ethanol at a temperature of from room temperature up to the boiling point of the oxidation mixture. 1 - Methyl - 5 - keto - dibenzocycloheptene is prepared by dehydrogenation of the cycloheptene compound using N-bromo succinimide. 1 - (2 - Methyl - 1,3 - dioxolan - 2 - yl) - 10,11- dihydro - 5H - dibenzocyclohepten - 5 - one is prepared by ketalization of the corresponding 1 -acetyl compound which is obtained by action of Mg diethylmalonate on the 1-chlorocarbonyl compound obtained by preparation of the acid chloride of 1 - carboxy - 10,11 - dihydro - 5H- dibenzocyclohepten-5-one obtained by cyclization of α,α<SP>1</SP>-bis-o-toluic acid prepared by hydrolysis of the dinitrile obtained by treatment of ocyanobenzyl chloride with Gilman alloy. Reference has been directed by the Comptroller to Specifications 986,577 and 858,186.