Water → 13-Methyl-17-methylene-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-3-ol

HRID 1367738Notes

Reaction equation

HRID 1367738 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.O>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1>[CH3:7][C:8]12[CH2:9][CH2:10][CH:11]3[CH:20]([CH2:19][CH2:18][C:17]4[CH:16]=[C:15]([OH:26])[CH:14]=[CH:13][C:12]=43)[CH:21]1[CH2:22][CH2:23][C:24]2=[CH2:1]

Participants

6

Reactant 3

HCID 962WaterHCID 5870EstroneHCID 23665647Potassium tert-butoxide

Product 1

HCID 1445855113-Methyl-17-methylene-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-3-olYield 11%

Reagents, catalysts & solvents 2

HCID 74505Methyltriphenyliphosphonium bromideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

Potassium tert-butoxide (220 mg, 1.96 mmol) was added to dry THF (5 ml) and stirred for 10 minutes to complete dissolution of the salt. Methyl triphenylphosphonium bromide (700 mg, 1.96 mmol) was added portionwise to the salt solution. Estrone (500 mg, 1.85 mmol) was dissolved in THF (5 ml) and added dropwise via a syringe to the bright yellow solution. After stirring at room temperature for 2 h, the reaction was heated at reflux overnight. The reaction was cooled, water added (10 ml) and the mixture extracted using ethyl acetate (3×10 ml). The combined organic fractions were combined, washed with water (2×10 ml) and brine (10 ml), dried (Na2SO4) and concentrated in vacuo. Flash column chromatography (SiO2 hexane:ethyl acetate 9:1) and recrystallisation from toluene/hexane afforded alkene 11 as a white crystalline solid (53 mg, 0.198 mmol, 11%). m.p. 130-132° C. (lit. m.p. 134-137° C.). δH (CDCl3) 0.82 (3H, s CH3), 1.20-1.62 (6H, m, alkyl H), 1.78-1.85 (1H, m, alkyl H), 1.90-1.99 (2H, m, alkyl H), 2.16-2.38 (3H, m, alkyl H), 2.50-2.59 (1H, m, alkyl H), 2.78-2.92 (2H, m, alkyl H), 4.50 (1H, s, OH), 4.67 (2H, t, J=2.0, olefinic H), 6.57 (1H, d, J=2.7, ArH-4), 6.63 (1H, dd, J=8.6, 2.7, ArH-2), 7.17 (1H, d, J=8.6, ArH-1).

Workup

  1. dissolutiondissolution of the salt
  2. additionadded dropwise via a syringe to the bright yellow solution
  3. stirringAfter stirring at room temperature for 2 h
  4. temperaturethe reaction was heated
  5. temperatureat reflux overnight
  6. temperatureThe reaction was cooled
  7. extractionthe mixture extracted
  8. washwashed with water (2×10 ml) and brine (10 ml)
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated in vacuo
  11. customFlash column chromatography (SiO2 hexane:ethyl acetate 9:1) and recrystallisation from toluene/hexane

Sources & evidence

ORD record
ord-1f5ef0b65dec4de98dbaa1f38d4f0239
Source dataset
uspto-grants-2011_02
Patent number
US07893284B2

Reaction notes

Loading…