Patent GB-1298212-A (GB)
Title: Novel isoxazole derivatives and a process for the preparation thereof
Inventor: SAUCY G
IPC: C07J1/00
Filed: 1969-11-20
Abstract: 1298212 Isoxazole-benzindene derivatives F HOFFMANN-LA ROCHE & CO AG 20 Nov 1969 [22 Nov 1968] 56791/69 Heading C2C The invention comprises compounds of the Formula I where Z is carbonyl, alkylene C 1-8 -dioxymethylene, di-alkoxy C 1-8 -methylene, phendioxy methylene or a group of the formula where R 7  is hydrogen, alkyl C 1-8 , alkoxy C 1-8 - alkyl C 1-8 , phenyl-alkyl C 1-8 , tetrahydropyranyl or acyl C 2-8 , R 8  is hydrogen or hydrocarbyl C 1-8 , m is 1 or 2; R 1  is a primaryl alkyl C 1-5  group, R 15  is hydrogen or alkyl C 1-8 , R 16  is hydrogen, alkyl C 1-8 , alkyl C 1-8 -aryl or aralkyl. They are prepared by cyclizing a compound of Formula II or alkylating a compound of Formula III with a 4-halomethylisoxazole. Compounds I where Z is a CHOH group may be prepared from the corresponding compounds where Z is a CHO-alkyl C 1-8  group. Trans - 4 - [3 - oxo - 5 - (3,5 - dimethyl - isoxazol - 4 - yl) - pentyl] - 1a - R 1  - perhydroindan- 1,5-dione, where R 1  is methyl or ethyl, is prepared by reacting chromium trioxide with trans- 3 - [2 - (3,5 - dimethyl - isoxazol - 4 - yl) - ethyl]- 6a - R 1  - perhydrocyclopenta[f][1]benzopyran - 4a, 7#-diol which is prepared from the action of sulphuric acid on trans-3-[2-(3,5-dimethylisoxazol - 4 - yl) - ethyl] - 6a - R 1  - 1,2,3,5,6,6a,7,8,9,- 9a - decahydrocyclopenta[f][1]benzopyran - 7# - ol which is prepared from the palladium-on-charcoal hydrogenation of the corresponding-1,2,3,- 5,6,6a,7,8 - octahydrocyclopenta[f][1]benzopyran- 7#-ol which is prepared from 2-(2-diethylaminoethyl) - 6 - [2 - (3,5 - dimethylisoxazol - 4 - yl)- ethyl] - tetrahydropyran - 2 - ol and 2 - methyl (or ethyl)-cyclopentane-1,3-dione. 2 - (2 - Diethylaminoethyl) - 6 - [2 - (3,5 - dimethylisoxazol - 4 - yl) - ethyl] - tetrahydropyran- 2-ol is prepared from diethylamine and 9-(3,5- dimethylisoxazol - 4 - yl) - 7 - hydroxynon - 1 - en-3-one. 7 - (3,5 - Dimethyl - isoxazol - 4 - yl) - 5 - hydroxyheptanoic acid lactone V is prepared from the corresponding heptenoic lactone which is prepared from the reaction of sulphuric acid on 3,5 - dimethyl - 4 - [2 - (3,4 - dihydro - 2H - pyran- 2-yl)-vinyl]-isoxazole IV which is prepared from acrolein dimer and (3,5 - dimethylisoxazol - 4- yl - methyl) - triphenyl - phosphonium chloride which is prepared from triphenylphosphine and 4 - chloromethyl - 3,5 - dimethyl - isoxazole which is prepared from the corresponding 4-hydroxymethyl compound which is prepared by the lithium aluminium hydride reduction of the corresponding 4-carboethoxy compound which is prepared from nitroethane, phosphorous oxychloride and ethyl #-pyrrolidinocrotonate which is prepared from pyrrolidine and ethyl acetoacetate. 3,5 - Dimethyl - 4 - [2 (6 - ethoxytetrahydropyran-2-yl)-ethyl]-isoxazole VI is prepared from the corresponding vinyl-isoxazole which is prepared from ethanol, sulphuric acid and IV above. 2 - (2 - Diethylaminoethyl) - 6 - [2 - (3,5 - dimethyl - isoxazol - 4 - yl) - ethyl] - tetrahydropyran- 2-ol is prepared from diethylamine, vinyl magnesium chloride and V above, which is prepared from 7 - (3,5 - dimethyl - isoxazol - 4 - yl) - 5 - oxoheptanoic acid which is prepared from 3,5-dimethyl - 4 - [2 - (6 - hydroxytetrahydropyran - 2- yl)-ethyl]-isoxazole which is prepared from VI above. (+) 19 - Nor - androst - 4 - en - 3,17 - dione is prepared by refluxing trans-anti-trans-3,3,7,7- bis - (ethylene - dioxy) - 3a - methyl - 6 - (3 - oxo - butyl)-perhydro-1H-benz[e]indene which is prepared by alkaline hydrolysis of the amide resulting from hydrogenation of trans-antitrans - 6 - [3,5 - dimethylisoxazol - 4 - yl)- methyl] - 3,3,7,7 - bis - (ethylenedioxy - 3amethyl perhydro-1H-benz[e]indene which is prepared from ethylene glycol and the hydrogenation product of I wherein Z is a carbonyl group.