Patent GB-803777-A (GB)
Title: Improvements in or relating to steroids and the manufacture thereof
IPC: C07J75/00
Filed: 1956-11-02
Abstract: The invention comprises a compound having the general formula <FORM:0803777/IV (b)/1> wherein the lower alkyl group contains from 1-8 C atoms, and a process for the production thereof which comprises oxidizing a 2-lower alkyl-3-keto-4-pregnen-20-ol having the general formula <FORM:0803777/IV (b)/2> wherein R is H or the acyl radical of an organic carboxylic acid containing from 1-8 C atoms inclusive, with chromic acid.  The 2-lower alkyl-3-keto-4-pregnen-20-ol or 20-ester thereof is obtained by treating 3-keto-4-pregnen-20-ol or a 20-ester thereof with a lower alkyl oxalate in the presence of an alkali metal base catalyst to obtain the alkali metal enolate of the corresponding 2 - lower - alkoxyoxalyl - 3 - keto - 4-pregnen-20-ol or the corresponding 20-ester thereof, which is reacted with an alkyl halide to obtain a 2 - lower - alkyloxyoxalyl - 2 - lower-alkyl - 3 - keto - 4 - pregnen - 20 - ol or a 20-ester thereof; this compound on hydrolysis with a base gives 2-lower alkyl-3-keto-4-pregnen-20-ol or a 20-ester thereof.  As alkali metal base catalysts there may be used sodium methoxide, sodium ethoxide, sodium isopropoxide, potassium methoxide, potassium t-butoxide and lithium methoxide, the alkali metals, the alkali metal hydrides, alkali metal amides, sodium amide and triphenyl methyl sodium.  Alkylation may be effected using methyl iodide, ethyl iodide, ethyl chloride, propyl bromide, isopropyl iodide, butyl iodide, butyl bromide, pentyl chloride, pentyl bromide, pentyl iodide, hexyl, heptyl and octyl chlorides bromides, iodides, phenyl bromide, phenyl iodide, benzyl chloride, bromide and iodide. Removal of the 2-lower-alkyloxyoxalyl may be effected with sodium ethoxide, potassium ethoxide, sodium methoxide, potassium methoxide and sodium or potassium hydroxide.  Oxidation is effected with chromic acid.  Examples disclose the preparation of 2-methyl, 2-ethyl and 2-butylprogesterone.  Also mentioned are 2-propyl-, 2-isobutyl-, 2-pentyl-, 2-hexyl-, 2-heptyl-, 2-octyl-, 2-benzyl and 2-phenylprogesterone.  Intermediates described in the examples are the sodium enolate of 2-ethoxyoxalyl-3-keto-4-pregnen-20-ol, potassium enolate of 2-methoxyoxalyl - 3 - keto - 4 - pregnen - 20 - ol 20 acetate, 2 - methoxyoxalyl - 3 - keto - 4 - pregnen-20b -ol 20b acetate and sodium enolate thereof, lithium enolate of 2-ethoxyoxalyl-3-keto-4-pregnen - 20b  - ol - 20b  - benzoate, sodium enolate of 2 - methoxyoxalyl - 3 - keto - 4-pregnen - 20b  - ol 20b - propionate, sodium enolate of 2 - methoxyoxalyl - 3 - keto - 4-pregnen - 20a  - ol 20 a  - butyrate, sodium enolate of 2 - methoxyoxalyl - 3 - keto - 4-pregnen - 20b  - ol 20b  - phenylacetate, sodium enolate of 2 - methoxyoxalyl - 3 - keto - 4-pregnen - 20 - ol 20 - phenylpropionate, potassium enolate of 2 - methoxyoxalyl - 3 - keto - 4-pregnen - 20 - ol valerate, 2 - methyl - 3 - keto-4 - pregnen - 20 - ol, 2 - ethyl - 3 - keto - 4 - pregnen - 20 - ol, 2 - propyl - 3 - keto - 4 - pregnen-20 - ol, 2 - benzyl - 3 - keto - 4 - pregnen - 20 - ol, 2 - butyl - 3 - keto - 4 - pregnen - 20 - ol and 2-methyl - 3 - keto - 4 - pregnen - 20b  - ol 20b -acetate.