Lithium diisopropylamide → HCID 15307278, compound

HRID 369054Notes

Reaction equation

HRID 369054 reaction equation
[F:1][CH:2](P(=O)(C1C=CC=CC=1)C1C=CC=CC=1)[F:3].C([N-]C(C)C)(C)C.[Li+].[O:26]1[CH2:31][CH2:30][CH2:29][CH2:28][CH:27]1[O:32][C:33]1[CH:50]=[CH:49][C:48]2[C:47]3[C@H:38]([C@H:39]4[C@@:43]([CH2:45][CH:46]=3)([CH3:44])[C:42](=O)[CH2:41][CH2:40]4)[CH2:37][CH2:36][C:35]=2[CH:34]=1>O1CCCC1.C(OCC)(=O)C.O>[F:1][C:2]([F:3])=[C:36]1[CH2:37][CH2:38][C@H:39]2[C@H:40]3[C:47](=[CH:46][CH2:45][C@:43]12[CH3:44])[C:48]1[CH:35]=[CH:34][C:33]([O:32][CH:27]2[CH2:28][CH2:29][CH2:30][CH2:31][O:26]2)=[CH:50][C:49]=1[CH2:42][CH2:41]3

Participants

7

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 15307277HCID 15307277, compoundHCID 15635908(Difluoromethyl)(oxo)diphenyl-lambda~5~-phosphane

Product 1

HCID 15307278HCID 15307278, compoundYield 42.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent2×

Procedure

A solution of 3.85 g of difluoromethyldiphenylphosphine oxide in 107 ml of tetrahydrofuran is slowly mixed with 7.6 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 2.14 g of 3-tetrahydropyranyloxy-estra-1,3,5(10),9(11)-tetraen-17-one in 42 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. 1.0 g of 17-difluoromethylene-3-tetrahydropyranyloxy-estra-1,3,5(10),9(11)-tetraene is obtained as a colorless oil, [α]D22 +52.6° (c=0.5% 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-133d7e55ac974d2a9128906a8c54adfb
Source dataset
uspto-grants-2000_10
Patent number
US06136800

Reaction notes

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