Ethyl Acetate → HCID 15307270, compound

HRID 369045Notes

Reaction equation

HRID 369045 reaction equation
[F:1][CH:2](P(=O)(C1C=CC=CC=1)C1C=CC=CC=1)[F:3].[CH:18]([N-]C(C)C)([CH3:20])[CH3:19].[Li+].[CH3:26][O:27][C@H:28]1[CH2:45][C@@:43]2([CH3:44])[C@@H:39]([CH2:40][CH2:41][C:42]2=O)[C@H:38]2[C@H:29]1[C:30]1[CH:31]=[CH:32]C(OC3CCCCO3)=C[C:35]=1[CH2:36][CH2:37]2.[C:54]([O:57][CH2:58][CH3:59])(=[O:56])[CH3:55]>O1CCCC1.O>[F:1][C:2]([F:3])=[C:42]1[CH2:41][CH2:40][C@H:39]2[C@H:38]3[C@H:29]([C@@H:28]([O:27][CH3:26])[CH2:45][C@:43]12[CH3:44])[C:30]1[CH:31]=[CH:32][C:58]([O:57][CH:54]2[CH2:55][CH2:20][CH2:18][CH2:19][O:56]2)=[CH:59][C:35]=1[CH2:36][CH2:37]3

Participants

7

Reactant 4

HCID 8857Ethyl Acetate2×HCID 2724682Lithium diisopropylamideHCID 10339998HCID 10339998, compoundHCID 15635908(Difluoromethyl)(oxo)diphenyl-lambda~5~-phosphane

Product 1

HCID 15307270HCID 15307270, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 3 g of difluoromethyldiphenylphosphine oxide in 80 ml of tetrahydrofuran is slowly mixed with 5.85 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 1.8 g of 11β-methoxy-3-tetrahydropyranyloxy-estra-1,3,5(10)-trien-17-one in 40 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 of 17-difluoromethylene-11β-methoxy-3-tetrahydropyranyloxy-estra-1,3,5(10)-triene is obtained with a melting point of 124-125° C., [α]D22 =+60.0° (c=0.505% 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 2.5 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/triethylamine

Sources & evidence

ORD record
ord-97051a27202b4fa69f5d01a5ed53edc1
Source dataset
uspto-grants-2000_10
Patent number
US06136800

Reaction notes

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