Reaktion #456241

ord-9104464ad15a4a029a275edb81d691a8

Reaktionsgleichung

C[C@H]1Cc2cc(OC3CCCCO3)ccc2[C@H]2CC[C@]3(C)C(=O)CC[C@H]3[C@@H]21
7β-methyl-3-tetrahydropyranyloxy-estra-1,3,5(10)-trien-17-one
O=P(c1ccccc1)(c1ccccc1)C(F)F
difluoromethyldiphenylphosphine oxide
CC(C)[N-]C(C)C.[Li+]
lithium diisopropylamide
→
C[C@H]1Cc2cc(OC3CCCCO3)ccc2[C@H]2CC[C@]3(C)C(=C(F)F)CC[C@H]3[C@@H]21
17-Difluoromethylene-7β-methyl-3-tetrahydropyranyloxy-estra-1,3,5(10)-triene

Edukte

C[C@H]1Cc2cc(OC3CCCCO3)ccc2[C@H]2CC[C@]3(C)C(=O)CC[C@H]3[C@@H]21
7β-methyl-3-tetrahydropyranyloxy-estra-1,3,5(10)-trien-17-one
O=P(c1ccccc1)(c1ccccc1)C(F)F
difluoromethyldiphenylphosphine oxide
CC(C)[N-]C(C)C.[Li+]
lithium diisopropylamide

Reagenzien

Keine

Lösungsmittel

CCOC(C)=O
ethyl acetate
O
water
C1CCOC1
tetrahydrofuran
CCOC(C)=O
ethyl acetate
C1CCOC1
tetrahydrofuran

Reaktionsbedingungen

Detaillierte Bedingungen
See reaction.notes.procedure_details.

Aufarbeitung

  1. 1
    workup.STIRRINGstirred for 15 minutes
  2. 2
    Temperaturslowly heated at a bath temperature of from -50° C. to 100° C.
  3. 3
    Temperaturrefluxed for 2.5 hours
  4. 4
    Waschenwashed with water as well as with saturated sodium chloride solution
  5. 5
    Sonstigedried on sodium sulfate
  6. 6
    Einengenconcentrated by evaporation in a vacuum
  7. 7
    Sonstigechromatographed on silica gel with hexane/ethyl acetate/triethylamine
  8. 8
    Sonstige1.3 g is obtained as colorless crystals with a melting point of 85-86° C., [α]D22 =-59-4° (c=0.535% in pyridine)

Vorschrift

A solution of 2 g of difluoromethyldiphenylphosphine oxide in 55 ml of tetrahydrofuran is slowly mixed with 3.9 ml of 2 M lithium diisopropylamide solution at a bath temperature of -50° C, and it is stirred for 1 hour. Then, a solution of 1.15 g of 7β-methyl-3-tetrahydropyranyloxy-estra-1,3,5(10)-trien-17-one in 20 ml of tetrahydrofuran is slowly added, stirred for 15 minutes, slowly heated at a bath temperature of from -50° C. to 100° C. and refluxed for 2.5 hours. For working-up, it is diluted with ethyl acetate and water, suctioned off on Celite, rewashed with ethyl acetate, washed with water as well as with saturated sodium chloride solution, dried on sodium sulfate, concentrated by evaporation in a vacuum and chromatographed on silica gel with hexane/ethyl acetate/triethylamine. 1.3 g is obtained as colorless crystals with a melting point of 85-86° C., [α]D22 =-59-4° (c=0.535% in pyridine).

Quelle

DOI: 10.6084/m9.figshare.5104873.v1Patent: US06136800uspto-grants-2000_10