Patent GB-944050-A (GB)
Title: 6-methylene-3-oxo-í¸-steroids and process for their preparation
Inventor: KIRK DAVID NEVILLE
IPC: C07J71/00
Filed: 1961-05-08
Abstract: The invention comprises (1) a process for the preparation of 6-methylene-3-oxo-D 4-steroids which comprises contacting with water or a nonanhydrous organic solvent corresponding steroids having the partial structure: <FORM:0944050/C2/1> (wherein only the 3, 4, 5, 6 and 7 positions of the steroid nucleus are shown, X is an anion and R1 is alkyl, cycloalkyl, hydroxyalkyl or aralkyl; and R11 is alkyl, cycloalkyl, aryl or aralkyl when R111 and RIV are hydrogen; or R11 is alkyl, R111 is aryl, aralkyl or alkyl and RIV is hydrogen or oxygen; or R11, R111 and RIV are alkyl; or R11 and R111 together with the nitrogen atom form a pyrrolidine, piperidine or morpholine ring and RIV is alkyl or oxygen) and (II) the specific new steroids, 6-methylene-19-nortestosterone and the b -phenylpropionate thereof, 6-methylenetestosterone b -phenylpropionate and 6-methylenedesoxycortiosterone.  When RIV in the above formula is oxygen an N1 oxide grouping exists, which may be expected in aqueous solutions to exist in the hydrated form -N(OH) R11R111\sJX\sK. Process (1) may be conducted by forming from a 6-dimethylaminomethyl steroid the corresponding metho bromide, methiodide or methosulphate which then decomposes in situ when, for example, methanol is used as solvent.  Other salts of the above partial structure also readily pass into 6-methylenic steroids and may therefore be formed in situ in the process of the invention.  The process is stated to be applicable to a wide variety of steroids such as those referred to in Specification 941,121 and including testololactone.  Examples describe the preparation of many 6-methylene steroids containing such groups as are detailed in the above mentioned Specification and in Specification 929,983.  6 - Dimethylaminoethyl - 17b  - hydroxy - 3 -methoxy - 17a  - methylandrosta - 3, 5 - diene is prepared by hydrolysis of the 17-propionate. itself prepared by decomposition of its borane complex-6 - Dimethylaminomethyl - 19 - nor - 3 - ethoxy -androst - 3, 5 - diene - 17b  - ol acetate is also prepared by decomposition of its borane complex. 3 - Ethoxy - 6 - dimethylaminomethyl - 17b -propionyloxy - 17a  - vinyl - androsta - 3, 5 - diene is prepared from the corresponding 6-unsubstituted compound and the Vilsmeier reagent followed by reduction. 3-Ethoxy-6-dimethylaminomethyl-17b  - propionyloxy - 17a  - prop - 11-ynylandrostra - 3, 5 - diene; 17a  - acetoxy - 6 -dimethylaminomethyl - 21 - fluoro - 3 - methoxypregna - 3, 5 - diene - 20 - one; 17a  - acetoxy - 6 -dimethylaminomethyl - 16a  - methyl - 3 - methoxypregna - 3, 5 - dien - 20 - one; 6 - dimethylaminomethyl - 3 - ethoxy - 2, 5D - spirosta - 3, 5 - diene; 3 - ethoxy - 6 - dimethylaminomethyl - 19 - norandrosta - 3, 5 - dien - 17b  - ol; 3 - methoxy - 17b -phenylpropionyloxy - 6 - dimethylaminomethyl - 19-nor - androsta - 3, 5 - diene; and 21 - acetoxy - 9a  -fluoro - 6 - dimethylaminomethyl - 11b , 17a  -dihydroxy - 3 - methoxypregna - 3, 5 - dien - 20-one are prepared similarly.  17a  - Acetoxy - 21 - fluoro - 3 - methoxypregna -3, 5 - dien - 20 - one and 3 - ethoxy - 19 - norandrosta - 3, 5 - dien - 17b  - ol are prepared by enol-arylation of the D 4-3-ketones.  17b  - Acetoxy - 6 - dimethylaminomethyl - 3 -ethoxy - androsta - 3, 5 - diene methosulphate is prepared from the free amine and dimethyl sulphate. 17b  - Acetoxy - 3 - methoxy - 6 - phenylaminomethylandrosta - 3, 5 - diene and the corresponding 17b -ol are prepared by reduction of the phenylimino compound, this being prepared from 17b -acetoxy - 6 - formyl - 3 - methoxyandrosta - 3, 5-diene and aniline.  3 - Methoxy - 17b  - phenylpropionyloxy - oestra-2, 5 (10) - diene is prepared from the 17b -ol and 3-phenylpropionyl chloride.  The N-oxide of 17a -acetoxy-6-dimethylaminomethyl-3-methoxy-pregna-3, 5-dien 20-one is prepared from the amine and H2O2.  Specifications 929,985 and 941,122 also are referred to.