Potassium Hydroxide → (17R)-spiro-[androstane-17,1'-cyclobutan]-2'-one

HRID 918031Notes

Reaction equation

HRID 918031 reaction equation
F[B-](F)(F)F.[OH-].[K+].O=C1CC[C@H]2[C@H:15]3[C@H:25](CC[C@]12C)[C@:23]1([CH3:24])[CH:18]([CH2:19][CH2:20][CH2:21][CH2:22]1)[CH2:17][CH2:16]3.F[B-](F)(F)F.C1([S+](C2C=CC=CC=2)C2C=CC=CC=2)CC1.CC(O[CH2:53][C:54]1[C:67]2[C:62](=C[CH:64]=[CH:65][CH:66]=2)[C:61]([CH2:68][O:69]C(C)=O)=[C:60]2[C:55]=1C=CC=C2)=O.F[B-](F)(F)F.[H+]>CS(C)=O>[C@@:67]12([CH2:66][CH2:65][C@H:64]3[C@H:15]4[C@H:25]([CH2:60][CH2:55][C@:54]13[CH3:53])[C@:23]1([CH3:24])[CH:22]([CH2:21][CH2:20][CH2:19][CH2:18]1)[CH2:17][CH2:16]4)[CH2:62][CH2:61][C:68]2=[O:69]

Participants

8

Reactant 6

HCID 14797Potassium Hydroxide2×HCID 26255TetrafluoroborateHCID 28118Tetrafluoroboric acidHCID 613145Acetic acid 10-acetoxymethyl-anthracen-9-ylmethyl esterHCID 2724210Cyclopropyldiphenylsulphonium tetrafluoroborateHCID 10880319Androstan-17-one

Product 1

HCID 22791389(17R)-spiro-[androstane-17,1'-cyclobutan]-2'-one

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

When carrying out the process of this invention, we prefer to utilize cyclopropylidiphenylsulfonium fluoroborate as reagent in dimethylsulfoxide as inert organic solvent and with powdered potassium hydroxide as the strong base. Usually, to a 17-oxo androstane devoid of other oxo functions (e.g. 3β-hydroxy-5-androstane-17-one) in an inert organic solvent (e.g. dimethylsulfoxide) there is added from about 1 to about 5 equivalents of the reagent containing an arylsulfurcyclopropane grouping (e.g. cyclopropyldiphenylsulfonium fluoroborate) and the reaction mixture is stirred under an inert atmosphere (e.g. under nitrogen) at room temperature for a few minutes. About 3 to 25 equivalents of powdered potassium hydroxide is then added, the reaction mixture stirred under an inert atmosphere for a few hours, then is poured into a large volume of ice water, and acetic or fluoroboric acid is added until the pH of the reaction mixture is at about pH 7 (i.e. treatment of the intermediate in situ with aqueous acid). The resulting (17R)-spiro-[androstane-17,1'-cyclobutan]-2'-one product (e.g. (17R)-spiro-[3β-hydroxy-5-androstene-17,1'-cyclobutan] -2'-one) is then isolated and purified utilizing techniques well known in the art; for example, by extraction with ethyl acetate, washing the combined organic solution with water, evaporation of the organic solution in vacuo to a residue followed by chromatography thereof.

Workup

  1. stirringthe reaction mixture stirred under an inert atmosphere for a few hours
  2. additionis added until the pH of the reaction mixture

Sources & evidence

ORD record
ord-a9c27bc226c5429ebe8556dbd8e67cc6
Source dataset
uspto-grants-1976_07
Patent number
US03968132

Reaction notes

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