PROCESS FOR PRODUCING 4A-ARYL-TRANS-DECAHYDRO-IZOQUINOLIN DERIVATIVES

摘要

1465223 Decahydroisoquinoline derivatives E I DU PONT DE NEMOURS & CO 22 Sept 1975 [23 Sept 1974 29 July 1975] 38836/75 Heading C2C The invention comprises compounds having the trans configuration of formula wherein R 1 is -CH 2 X, where X is C 2 to C 6 alkenyl or C 2 to C 6 alkynyl where m is 1 or 2; R2 is divalent oxygen or together with the nuclear carbon atom to which it is attached forms the group R3 is H, OH, OCH 3 , OCOCH 3 , or F; and R4 is H, OH, OCH 3 , or OCOCH 3 , provided that when R3 is F, R4 must be H; and pharmaceutically acceptable salts thereof. Compounds of Formula I having the general formula wherein R5 is and Ar1 is where R 9 is H, F or OCH 3 , and R10 is H or OCH 3 , provided that when R9 is F, R10 is H, may be prepared by reaction of a compound of the formula with R1X (where X is Br, I or an organic sulphonate group) under basic conditions. The starting material of formula (b) may be prepared by the steps of (a) reacting a compound of the formula with an anhydrous alcohol R6OH (R6 is C 1 to C 4 alkyl) at 50‹ to 120‹ C. in the presence of HCl under inert anhydrous conditions to form a compound of the formula (b) heating product (2) with sodium hydride and benzyl bromide to form (c) reacting product (3) with hydrogen in the presence of a reducing catalyst to form (d) refluxing product (4) with lithium aluminium hydride to form and (e) reacting product (5) with a hydrocarbyl- or chlorohydrocarbylchloroformate at from -10‹ to + 50‹ C. and hydrolysing to produce a compound of Formula (6). The compounds of Formula I exhibit analgesic activity and may be administered orally, parenterally or rectally preferably in admixture with a pharmaceutically suitable carrier.