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

HRID 850843Notes

Reaction equation

HRID 850843 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-f281c84a6a7f4cc8b858e66a420bcc7b
Source dataset
uspto-grants-2000_01
Patent number
US06018062

Reaction notes

Loading…