Tetrahydrofuran → 3alpha-Acetylthio-6-methyleneandrostan-17-one

HRID 42131Notes

Reaction equation

HRID 42131 reaction equation
[C:1]([S:4][C@@H:5]1[CH2:22][CH2:21][C@@:20]2([CH3:23])[CH:7]([C:8](=O)[CH2:9][C@@H:10]3[C@@H:19]2[CH2:18][CH2:17][C@@:15]2([CH3:16])[C@H:11]3[CH2:12][CH2:13][C:14]2=[O:24])[CH2:6]1)(=[O:3])[CH3:2].[CH2:26]1COCC1>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:1]([S:4][C@@H:5]1[CH2:22][CH2:21][C@@:20]2([CH3:23])[CH:7]([C:8](=[CH2:26])[CH2:9][C@@H:10]3[C@@H:19]2[CH2:18][CH2:17][C@@:15]2([CH3:16])[C@H:11]3[CH2:12][CH2:13][C:14]2=[O:24])[CH2:6]1)(=[O:3])[CH3:2].[SH:4][C@@H:5]1[CH2:22][CH2:21][C@@:20]2([CH3:23])[CH:7]([C:8](=[CH2:26])[CH2:9][C@@H:10]3[C@@H:19]2[CH2:18][CH2:17][C@@:15]2([CH3:16])[C@H:11]3[CH2:12][CH2:13][C:14]2=[O:24])[CH2:6]1

Participants

5

Reactant 2

HCID 8028Tetrahydrofuran2×HCID 866355963alpha-Acetylthioandrostane-6,17-dione

Product 2

HCID 866355983alpha-Acetylthio-6-methyleneandrostan-17-oneYield 35%HCID 866355993alpha-Mercapto-6-methyleneandrostan-17-oneYield 35%

Reagents, catalysts & solvents 1

HCID 74505Methyltriphenyliphosphonium bromideCatalyst

Procedure

To a stirred solution of 3α-acetylthioandrostane-6,17-dione (600 mg) in THF (8 mL) cooled at −50° C., a solution of ylide prepared from methyltriphenylphosphonium bromide (1.47 g) in THF dry (8 mL) at −50° C. and potassium tert-butoxide (484 mg), was added. After 2 h the temperature was raised to room temperature. The mixture was quenched by addition of 5% NaH2PO4 aqueous solution and extracted with EtOAc (2×60 mL). The combined organic extracts were washed with 5% NaH2PO4 aqueous solution, brine, dried over Na2SO4, and evaporated to dryness. The residue was purified by flash chromatography (n-hexane/EtOAc 9/1) to give 3α-acetylthio-6-methyleneandrostan-17-one (210 mg, 35% yield) and 3α-mercapto-6-methyleneandrostane-17-one (208 mg, 35% yield). 1H-NMR (300 MHz, DMSO-d6, ppm from TMS): 3α-acetylthio-6-methyleneandrostane-17-one: δ 4.73 (1H, m), 4.39 (1H, m), 3.96 (1H, m), 2.44-0.84 (20H, m), 2.29 (3H, s), 0.75 (3H, s), 0.66 (3H, s); 3α-mercapto-6-methyleneandrostane-17-one: δ 4.73 (1H, m), 4.38 (1H, m), 3.57 (1H, m), 2.52 (1H, d), 2.45-0.95 (20H, m), 0.76 (3H, s), 0.63 (3H, s).

Workup

  1. customdry (8 mL) at −50° C.
  2. additionpotassium tert-butoxide (484 mg), was added
  3. customThe mixture was quenched by addition of 5% NaH2PO4 aqueous solution
  4. extractionextracted with EtOAc (2×60 mL)
  5. washThe combined organic extracts were washed with 5% NaH2PO4 aqueous solution, brine
  6. dry with materialdried over Na2SO4
  7. customevaporated to dryness
  8. customThe residue was purified by flash chromatography (n-hexane/EtOAc 9/1)

Sources & evidence

ORD record
ord-f4ee1d3237284005ab3c529d73016313
Source dataset
uspto-grants-2013_09
Patent number
US08536160B2

Reaction notes

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