Patent GB-1265512-A (GB)
Inventor: HAJOS Z G
IPC: C07D317/26
Filed: 1969-10-02
Abstract: 1,265,512. Tricyclic ketones. F. HOFFMANN-LA ROCHE & CO. A.G. 2 Oct., 1969 [4 Oct., 1968; 28 July, 1969], No. 48385/69. Headings C2C and C2U. Novel tricyclic ketones of the formula in which m is 1 or 2, B represents carboxy, C 1-7  -alkoxycarbonyl, aryloxycarbonyl, cyano, C 1-7  alkylsulphinyl or C 1-7  alkylsulphonyl, Z represents carbonyl, C 1-6  alkylenedioxymethylene or a group >CHOR 2  (where R 2  is hydrogen, C 1-7  alkyl, C 1-7  alkoxy-C 1-7  alkyl, phenyl- C 1-7  alkyl, tetrahydropyranyl, C 1-6  alkanoyl, benzoyl, nitrobenzoyl, barboxy-C 1-6  alkanoyl, carboxybenzoyl, trifluoromethyl or camphor sulphonyl), R 4  is hydrogen or C 1-7  alkyl and R 1  is hydrogen, C 1-7 - alkyl or a group of the formulae (where R 7  is C 1-7  alkyl, R 15  is an oxo, C 1-6  alkylenedioxy or arylendioxy group or represent hydrogen and a C 1-7  alkoxy group, R 25  and R 26  are hydrogen, hydroxy or C 1-7  alkyl, R<SP>1</SP> is hydrogen or C 1-7  alkyl and R<SP>11</SP> is hydrogen, C 1-7  alkyl, C 1-7  alkylaryl or aralkyl) and the alkali metal salts of the free acids, are prepared by treating a compound of the formula in an inert organic solvent with a dilute solution of an alkali metal or alkaline earth metal hydroxide to effect cyclization and, if required acidifying a product in which B is the salt of a carboxy group to the free acid or esterifying a product in which B is a carboxy group. Examples describe the preparation of the 6-methyl-, 6 - [2 - (2 - methyl - 1,3 - dioxolan - 2 - yl)ethyl]-, 6 - [(3,5 - dimethyl - isoxazol - 4 - yl)methyl]-, 6 - (3,3 - phenylenedioxybutyl) - derivatives of 3# - t butoxy - 2,3,3a,4,5,7,8,9,9a#,9bα- decahydro - 3a#- methyl - 7 - oxo - 1H- benz[e]- inden - 8α - carboxylic acid and the methyl ester thereof. Steroids.-The novel ketones are used in the preparation of steroids. Thus, ketals of the formula where W is an alkylene or arylene radical, can be decarboxylated by heating to ketals of the formula catalytically hydrogenated to  and cyclized to the steroids of the formula Examples 2 and 4 describe the preparation of racemic 19-nortestosterone by this route, and it is also stated that a product wherein R 4  is Et, may then be oxidized and ethynylated to yield optically active norgestrel. Also, ketones of the formula can be decarboxylated by,heating to compounds and cyclized using an alkali alkoxide to diene steroids of the formula or the ketones of the formula Ib can be treated with a base to obtain acids of the formula which on heating with cone. mineral acid yield hydroxy diene steroids of the formula which can also be obtained from the steroids VII by refluxing in methanol/HCl. Further, ketones of the Formula I in which R 1  is an isoxazolylmethyl group can be decarboxylated to the compounds Ic and subsequently converted to 19-norsteroids as shown below In Example 3 a compound of Formula X wherein Z is carbpnyl is converted to its bis-(ethylene) ketal which is then hydrogenated to yield a "vinylogous amide" of unspecified structure. The latter is refluxed with aqueous KOH and the resulting 3,3;7,7 - bis - (ethylenedioxy)- 3a# - methyl - 6 - (3 - oxobutyl) - perhydro - 1H- benz[e]indene is cyclized with aqueous HCl to yield estr-4-ene-3,17-dione. In the preparation of steroids, the 6 - methyl - 6 - [2 - (2 methyl - 1,3- dioxolan - 2 - yl)ethyl]-, and 6 - [(3,5 - dimeihylisoxazol - 4 - yl)methyl] and 6 - (3,3 - diphenylenedioxyliutyl) - derivatives of 3# - t - butoxy- 2,3,3a,4,5,7,8,9,9a#,9b# - dehydro - 3a# - methyl- 1H - benz[e]inden - 7 - one, and the corresponding dodecahydro compounds, 6 - [3,5 - dimethyl - 4- isoxazolyl)methyl] - 3a# - methyl - 3# - hydroxy- 1,2,3,3a,4,5,8,9,9a#,9bα - decahydro - 7H- benz[e]inden - 7 - one, 6 - [(3,5 - dimethyl - -.4- isoxazolyl)methyl] - 3a# - methyl - 1,2,3,3a,4,5,9, 9a#,9bα - octahydro - 3H benz[e]inden - 3,7(8H)- dione, and the corresponding 2H,6H saturated dione and its di-ethylene ketal, and 3,3,7,7-bis- (ethylenedioxy) - 3a# - methyl - 6 - (3 - oxobutyl)- perhydro - 1H - benz[e]indene are obtained.