Lithium diisopropylamide → 17-Difluoromethylene-3-methoxy-18-methyl-estra-1,3,5(10)-triene

HRID 369064Notes

Reaction equation

HRID 369064 reaction equation
C(OP([CH:9]([F:11])[F:10])(=O)OCC)C.C([N-]C(C)C)(C)C.[Li+].[CH3:20][O:21][C:22]1[CH:40]=[CH:39][C:38]2[C@@H:37]3[C@H:27]([C@H:28]4[C@@:32]([CH2:35][CH2:36]3)([CH2:33][CH3:34])[C:31](=O)[CH2:30][CH2:29]4)[CH2:26][CH2:25][C:24]=2[CH:23]=1>O1CCCC1.C(OCC)(=O)C>[F:11][C:9]([F:10])=[C:31]1[CH2:30][CH2:29][C@H:28]2[C@H:27]3[C@H:37]([CH2:36][CH2:35][C@:32]12[CH2:33][CH3:34])[C:38]1[CH:39]=[CH:40][C:22]([O:21][CH3:20])=[CH:23][C:24]=1[CH2:25][CH2:26]3

Participants

6

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 2758305Phosphonic acid, (difluoromethyl)-, diethyl esterHCID 11087833Ethylmetrienone

Product 1

HCID 7019755717-Difluoromethylene-3-methoxy-18-methyl-estra-1,3,5(10)-trieneYield 80.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 9.4 g of diethyl-(difluoromethyl)-phosphonate in 150 ml of tetrahydrofuran is slowly mixed with 25 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 6 g of 3-methoxy-18-methyl-estra-1,3,5(10)-trien-17-one in 173 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 6 hours. For working-up, it is diluted 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. 5.4 g of 17-difluoromethylene-3-methoxy-18-methyl-estra-1,3,5(10)-triene is obtained as colorless crystals with a melting point of 145-146° C., [α]D22 =+40.2° (c=0.515% in pyridine).

Workup

  1. stirringstirred for 15 minutes
  2. temperatureslowly heated at a bath temperature of from -50° C. to 100° C.
  3. temperaturerefluxed for 6 hours
  4. washwashed with water as well as with saturated sodium chloride solution
  5. customdried on sodium sulfate
  6. concentrationconcentrated by evaporation in a vacuum
  7. customchromatographed on silica gel with hexane/ethyl acetate

Sources & evidence

ORD record
ord-11ea0b66c8bc41acb13e42b0f92971f3
Source dataset
uspto-grants-2000_10
Patent number
US06136800

Reaction notes

Loading…