Ethanol → 11beta-Fluoro-17beta-hydroxy-7alpha-methylestr-4-en-3-one

HRID 900676Notes

Reaction equation

HRID 900676 reaction equation
[F:1][C@H:2]1[CH2:19][C@@:17]2([CH3:18])[C@@H:13]([CH2:14][CH2:15][C:16]2=[O:20])[C@H:12]2[C@H:3]1[C@@H:4]1[C:9]([CH2:10][C@H:11]2[CH3:21])=[CH:8][C:7](=[O:22])[CH2:6][CH2:5]1.C(O)C.O.[BH4-].[Na+]>O1CCCC1>[F:1][C@H:2]1[CH2:19][C@@:17]2([CH3:18])[C@@H:13]([CH2:14][CH2:15][C@@H:16]2[OH:20])[C@H:12]2[C@H:3]1[C@@H:4]1[C:9]([CH2:10][C@H:11]2[CH3:21])=[CH:8][C:7](=[O:22])[CH2:6][CH2:5]1

Participants

6

Reactant 4

HCID 702EthanolHCID 962WaterHCID 4311764Sodium borohydride2×HCID 10193144HCID 10193144, compound

Product 1

HCID 990463811beta-Fluoro-17beta-hydroxy-7alpha-methylestr-4-en-3-oneYield 45.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-55 °C

Procedure

A solution of 500 mg of 11β-fluoro-7α-methylestr-4-ene-3,17-dione (B′) in 10 ml of tetrahydrofuran, 5.8 ml of ethanol and 1.15 ml of water was stirred at −55° C. with 175.6 mg of sodium borohydride for 2.5 hours. After another 351.2 mg of sodium borohydride was added, it was stirred for another 1.5 hours at −55° C., then added to ice water, extracted three times with ethyl acetate, washed neutral, dried on sodium sulfate and concentrated by evaporation in a vacuum. Then, it was chromatographed on silica gel with hexane/ethyl acetate. 230 mg of pure 11β-fluoro-17β-hydroxy-7α-methylestr-4-en-3-one (I) with a melting point of 126.7° C. was obtained ([α]D20=+79.9° (c=0.53% in chloroform)).

Workup

  1. extractionextracted three times with ethyl acetate
  2. washwashed neutral
  3. customdried on sodium sulfate
  4. concentrationconcentrated by evaporation in a vacuum
  5. customThen, it was chromatographed on silica gel with hexane/ethyl acetate

Sources & evidence

ORD record
ord-5b82b0216cbd47ae94593b3bcda12e68
Source dataset
uspto-grants-2008_04
Patent number
US07361645B2

Reaction notes

Loading…