Lithium diisopropylamide → 17-Difluoromethylene-7beta-methyl-3-tetrahydropyranyloxy-estra-1,3,5(10)-triene

HRID 369059Notes

Reaction equation

HRID 369059 reaction equation
[F:1][CH:2](P(=O)(C1C=CC=CC=1)C1C=CC=CC=1)[F:3].C([N-][CH:22]([CH3:24])[CH3:23])(C)C.[Li+].C[C@H]1C[C:43]2[CH:42]=[C:41]([O:45][CH:46]3[CH2:51][CH2:50][CH2:49][CH2:48][O:47]3)[CH:40]=[CH:39][C:38]=2[C@@H:37]2[C@@H:28]1[C@H:29]1[C@@:33]([CH2:35][CH2:36]2)([CH3:34])[C:32](=O)[CH2:31][CH2:30]1>O1CCCC1.C(OCC)(=O)C.O>[F:1][C:2]([F:3])=[C:32]1[CH2:31][CH2:30][C@H:29]2[C@H:28]3[C@H:37]([CH2:36][CH2:35][C@:33]12[CH3:34])[C:38]1[CH:43]=[CH:42][C:41]([O:45][CH:46]2[CH2:51][CH2:50][CH2:49][CH2:48][O:47]2)=[CH:40][C:39]=1[CH2:24][C@@H:22]3[CH3:23]

Participants

7

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 15635908(Difluoromethyl)(oxo)diphenyl-lambda~5~-phosphaneHCID 183970847beta-Methyl-3-tetrahydropyranyloxy-estra-1,3,5(10)-trien-17-one

Product 1

HCID 1839708317-Difluoromethylene-7beta-methyl-3-tetrahydropyranyloxy-estra-1,3,5(10)-triene

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent2×

Procedure

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).

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
  8. custom1.3 g is obtained as colorless crystals with a melting point of 85-86° C., [α]D22 =-59-4° (c=0.535% in pyridine)

Sources & evidence

ORD record
ord-9104464ad15a4a029a275edb81d691a8
Source dataset
uspto-grants-2000_10
Patent number
US06136800

Reaction notes

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