Estrone → 17-Methylene-estra-1,3,5(10)-trien-3-ol

HRID 1781940Notes

Reaction equation

HRID 1781940 reaction equation
[CH3:1]C(C)([O-])C.[K+].[CH3:7][C@@:8]12[C:24](=O)[CH2:23][CH2:22][C@H:21]1[C@H:20]1[C@@H:11]([C:12]3[CH:13]=[CH:14][C:15]([OH:26])=[CH:16][C:17]=3[CH2:18][CH2:19]1)[CH2:10][CH2:9]2>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CS(C)=O>[CH2:1]=[C:24]1[CH2:23][CH2:22][C@H:9]2[C@H:10]3[C@H:11]([CH2:20][CH2:21][C@:8]12[CH3:7])[C:12]1[CH:13]=[CH:14][C:15]([OH:26])=[CH:16][C:17]=1[CH2:18][CH2:19]3

Participants

5

Reactant 2

HCID 5870EstroneHCID 23665647Potassium tert-butoxide

Product 1

HCID 1445855217-Methylene-estra-1,3,5(10)-trien-3-olYield 76.3%

Reagents, catalysts & solvents 2

HCID 74505Methyltriphenyliphosphonium bromideCatalystHCID 679Dimethyl SulfoxideSolvent2×

Procedure

A suspension of methyltriphenylphosphonium bromide (100.03 g, 0.28001 mol) and potassium t-butoxide (31.42 g, 0.2800 mol) in anh. dimethylsulfoxide (DMSO, 320 mL) under argon was stirred in an oil bath (68°-81° C.) 1 h, after which estrone (15.14 g, 55.99 mmol) in anh. DMSO (320 mL) was added via syringe. See FIG. 17. Stirring was continued 1 h and the reaction allowed to cool. The mixture was poured into 800 mL of ice-1N hydrochloric acid and then extracted three times with 400 mL aliquots of ether. The combined organic extracts were washed with 350 mL of saturated sodium bicarbonate+400 mL of brine, dried over sodium sulfate, and flash filtered through a 58 mm high×84 mm dia. column of silica gel (200-40 mesh). Product continued eluting with additional ether. Concentration of appropriate fractions under reduced pressure and three-fold recrystallization from aqueous ethanol gave very fine white needles (11.47 g, 42.73 mmol, 76%), m.p. 134°-136° C., homogeneous to TLC (20% ethyl acetate/hexanes on silica gel, Rf 0.45). (NA-1994A-242B)

Workup

  1. stirringStirring
  2. waitwas continued 1 h
  3. temperatureto cool
  4. extractionextracted three times with 400 mL aliquots of ether
  5. washThe combined organic extracts were washed with 350 mL of saturated sodium bicarbonate+400 mL of brine
  6. dry with materialdried over sodium sulfate, and flash
  7. filtrationfiltered through a 58 mm high×84 mm dia
  8. washProduct continued eluting with additional ether
  9. customConcentration of appropriate fractions under reduced pressure and three-fold recrystallization from aqueous ethanol

Sources & evidence

ORD record
ord-f5acae62e6b3429fbdd22b19dd4f3794
Source dataset
uspto-grants-1997_05
Patent number
US05633392

Reaction notes

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