Reaction equation
[CH3:1][C@@:2]12[C:10](=[O:11])[CH2:9][CH2:8][C@H:7]1[C@@H:6]1[CH2:12][CH:13]=[C:14]3[CH2:19][C@@H:18]([OH:20])[CH2:17][CH2:16][C@:15]3([CH3:21])[C@H:5]1[CH2:4][CH2:3]2.[H-].[Na+].[CH2:24](Cl)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>>[CH2:24]([O:20][CH:18]1[CH2:17][CH2:16][C@@:15]2([CH3:21])[C:14](=[CH:13][CH2:12][C@@H:6]3[C@@H:5]2[CH2:4][CH2:3][C@@:2]2([CH3:1])[C@H:7]3[CH2:8][CH2:9][C:10]2=[O:11])[CH2:19]1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1Participants
Procedure
3β-Benzyloxyandrost-5-en-17β-thiol is obtained starting from dehydroepiandrosterone. The dehydroepiandrosterone is reacted with one equivalent of sodium hydride and benzyl chloride by standard procedures for making benzyl ethers to give 3-benzyloxyandrost-5-en-17-one. This benzyloxy compound is then reacted with Lawesson's reagent (4-methoxyphenylthiophosphine sulfide dimer) according to the procedure described in M. Feiser, "Feiser and Feiser's Reagents for Organic Synthesis", John Wiley & Sons, New York, 1980, p. 327; also B. S. Pedersen et al., Bull. Soc. Chim. Belg., 87, 223 (1978). This gives 3β-benzyloxyandrost-5-ene-17-thione and this thione is then reduced with lithium aluminum hydride by standard procedures to give the desired 17β-thiol. Then, to a solution of cyclopropanone in dichloromethane under nitrogen at -50° C., there is added rapidly 1.1 equivalent of the above thiol in dichloromethane. The temperature is allowed to rise to -30° C. and, after 16 hours, most of the solvent is evaporated. Dry ether is added to precipitate by-product polyketene. The by-product is removed by filtration, the solvent is distilled from the filtrate, and the residue is purified by flash chromatography to give 3β-benzyloxy-17β-(1-hydroxycyclopropylthio)androst-5-ene.
Sources & evidence
- ORD record
- ord-3687f236a13f49e9a3686d27724bbc17
- Source dataset
- uspto-grants-1990_01
- Patent number
- US04891367
Linked notes
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