Process for the preparation of 9 beta,10 alpha-progesterone (retroprogesterone)
AssigneeIndustriale Chimca S.R.L.
InventorsRoberto Lenna, Claudio Delfrate, Davide Rigamonti
Life of this patent
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Abstract
The present invention refers to a new process for the synthesis of (9β,10α)-pregn-4-ene-3,20-dione, commonly known as retroprogesterone, having the formula (1) shown below.
Claims5
Process for the synthesis of retroprogesterone, comprising the following steps:
- a) reaction of compound (7), (3S,3aS,5aR,6R,9aR,9bS)-3-((S)-1-hydroxyethyl)-3a,6-dimethyldodecahydro-7H-cyclopenta[a]naphthalen-7-one, with acrylonitrile to yield compound (6), 3-((3S,3aS,5aR,6S,9aS,9bS)-3-((S)-1-hydroxyethyl)-3a,6-dimethyl-7-oxododecahydro-1H-cyclopenta[a]naphthalen-6-yl)propanenitrile:
- b) reaction of compound (6) with a strong base to yield compound (5), 3-((3S,3aS,5aR,6S,9aS,9bS)-3-((S)-1-hydroxyethyl)-3a,6-dimethyl-7-oxododecahydro-1H-cyclopenta[a]naphthalen-6-yl)propanoic acid:
- c) reaction of compound (5) with acetic anhydride, Ac2O, to yield compound (4), (S)-1-((4aS,4bR,6aS,7S,9aS,9bS)-4a,6a-dimethyl-2-oxo-2,3,4,4a,4b,5,6,6a,7,8,9,9a,9b,10-tetradecahydroindeno[5,4-f]chromen-7-yl)ethyl acetate:
- d) reaction of compound (4) with a C1 organometallic reagent to yield compound (3), (S)-1-((3S,3aS,5aR,6S,9aS,9bS)-3a,6-dimethyl-7-oxo-6-(3-oxobutyl)dodecahydro-1H-cyclopenta[a]naphthalen-3-yl)ethyl acetate:
- wherein by “C1 organometallic reagent” is meant an organometallic compound in which the organic moiety comprises only one carbon atom;
- e) reaction of compound (3) with a strong base to yield compound (2), (8S,9R,10S,13S,14S,17S)-17-((S)-1-hydroxyethyl)-10,13-dimethyl-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-3H-cyclopenta[a]phenanthren-3-one:
- f) oxidation of intermediate (2) to obtain retroprogesterone:
3-((3S,3aS,5aR,6S,9aS,9bS)-3-((S)-1-hydroxyethyl)-3a,6-dimethyl-7-oxododecahydro-1H-cyclopenta[a]naphthalen-6-yl)propanenitrile, compound of formula (6):
3-((3S,3aS,5aR,6S,9aS,9bS)-3-((S)-1-hydroxyethyl)-3a,6-dimethyl-7-oxododecahydro-1H-cyclopenta[a]naphthalen-6-yl)propanoic acid, compound of formula (5):
(S)-1-((4aS,4bR,6aS,7S,9aS,9bS)-4a,6a-dimethyl-2-oxo-2,3,4,4a,4b,5,6,6a,7,8,9,9a,9b, 10-tetradecahydroindeno[5,4-f]chromen-7-yl)ethyl acetate, compound of formula (4):
(S)-1-((3S,3aS,5aR,6S,9aS,9bS)-3a,6-dimethyl-7-oxo-6-(3-oxobutyl)dodecahydro-1H-cyclopenta[a]naphthalen-3-yl)ethyl acetate, compound of formula (3):
Dependencies are inferred from the claim text.