Patent IE-33651-B1 (IE)
Title: A process for the manufacture of 19-norsteroids
Inventor: SAUCY G
IPC: C07F9/54
Filed: 1969-11-21
Abstract: 1298211 Isoxazole derivatives F HOFFMANN-LA ROCHE & CO AG 20 Nov 1969 [22 Nov 1968] 56790/69 Heading C2C The invention comprises isoxazole compounds of the Formula I where R 15 is a hydrogen atom or alkyl C 1-8 radical, R 16 is a hydrogen atom or alkyl C 1-8 , aryl-alkyl C 1-8 or alkyl C 1-8 -ary] radical and R 17 is a vinyl, 2-chloro-ethyl, 2-hydroxyethyl, 2- alkoxy C 1-8 -ethyl, monohydrocarbyl-aminoethyl or dihydrocarbyl-amino-ethyl radical, cyclic hemiketals of such compounds in which R 17 represents a mono or di-hydrocarbyl-aminoethyl radical and acid addition salts thereof. They are prepared by reacting a 7-(3-R 15 , 5-R 16 -isoxazol-4-yl)- 5-hydroxy-heptanoic acid lactone with a vinyl magnesium halide at a low temperature in an inert organic solvent to form a compound I in which R 17 is a vinyl group or by selectively oxidizing a 9-(3-R 15 , 5-R 16 -isoxazol-4- yl)-3,7-dihydroxy-non-1-ene to form a compound I where R 17 is a vinyl group and, if desired, converting the vinyl group to the other radicals represented by R 17 by known methods. (+) 19 - Nor - androst - 4 - en - 3,17 - dione is prepared by reacting hydrochloric acid with trans - anti - trans - 3,3;7,7 - bis - (ethylenedioxy)- 3a - methyl - 6 (3 - oxobutyl) - perhydro - 1H- benz[e]indene which is prepared by treating with alkali the reduced (Pd on C) reaction product of trans - anti - trans - 6 - [(3,5 - dimethylisoxazol - 4 - yl) - methyl] - 3,3;7,7 - bis - (ethylenedioxy) - 3a - methyl - perhydro - 1H - benz[e]- indene which is prepared by reacting ethylene glycol with trans-anti-trans-6-[(3,5-dimethylisoxazol - 4 - yl) - methyl] - 3a - methyl - 3a,4,5,5a,8,- 9,9a,9b - octahydro - 1H - benz[e] - inden - 3,7- (2H,6H)-dione, which is prepared by CrO 3 oxidation of ( - ) trans - anti - 6 [(3,5 - dimethylisoxazol - 4 - yl) - methyl] - 3a methyl - 3# - hydroxy- 1,2,3,3a,4,5,8,9,9a,9b - decahydro - 7H - benz[e]- inden-7-one which is prepared by hydrolysis of the corresponding 3#-tert.-butoxy compound which is prepared by reacting (+) trans-anti-3amethyl- 3# - tert.-butoxy-1,2,3,3a,4,5,8,9,9a,9bdecahydro - 7H benz[e]indene - 7 - one with 4-chloromethyl-3,5-dimethylisoxazole. (+) Trans - anti - 6 - [(3,5 - dimethylisoxazol- 4 - yl) - methyl] - 3a - methyl - 1,2,3a,4,5,9,9a,9boctahydro - 3H - benz[e]indene - 3,7(8H) - dione is prepared by reacting sodium hydroxide with trans - 4 - [3 - oxo - 5 - (3,5 - dimethylisoxazol - 4- yl) - pentyl] - 1a - methyl - perhydroindan - 1,5- dione which is prepared by reacting sulphuric acid with trans - 3 - [2 - (3,5 - dimethylisoxazol- 4 - yl) - ethyl] - 6a - methyl - perhydrocyclopenta- [f][1]benzopyran-4a,7b-diol which is prepared by sulphuric acid oxidation of the corresponding 1,2,3,5,6,6a,7,8,9,9a - decahydrocyclopenta[f][1]- benzopyran-7#-ol which is prepared by lithium aluminium hydride reduction of the corresponding 1,2,3,5,6,6a - hexahydrocyclopenta[f][1]- benzopyran-7(8H)-one which is prepared by reacting 2 - methyl - cyclopentane - 1,3 - dione, and ( - ) 2 - (2 - ( - ) - α - phenethylaminoethyl- 6 - [2 - (3,5 - dimethylisoxazol - 4 - yl) - ethyl]- tetrahydropyran-2-ol-oxalate.
[GB1298211A]