Cerium(III) chloride → 17alpha-Ethinyl-11beta-fluoro-17beta-hydroxy-7alpha-methylestr-4-en-3-one

HRID 855483Notes

Reaction equation

HRID 855483 reaction equation
[Cl-].[Ce+3].[Cl-].[Cl-].[C:5]([Mg]Br)#[CH:6].[F:9][C@H:10]1[CH2:27][C@@:25]2([CH3:26])[C@@H:21]([CH2:22][CH2:23][C:24]2=[O:28])[C@H:20]2[C@H:11]1[C@@H:12]1[C:17](=[CH:18][C@H:19]2[CH3:29])[CH:16]=[C:15]([O:30]C)[CH2:14][CH2:13]1.[Cl-].[NH4+]>O1CCCC1.O>[C:5]([C@:24]1([OH:28])[CH2:23][CH2:22][C@H:21]2[C@H:20]3[C@H:11]([C@@H:10]([F:9])[CH2:27][C@:25]12[CH3:26])[C@@H:12]1[C:17](=[CH:16][C:15](=[O:30])[CH2:14][CH2:13]1)[CH2:18][C@H:19]3[CH3:29])#[CH:6]

Participants

7

Reactant 4

HCID 24636Cerium(III) chlorideHCID 25517Ammonium ChlorideHCID 6933295211beta-Fluoro-3-methoxy-7alpha-methylestra-3,5-dien-17-oneHCID 178418486HCID 178418486, compound

Product 1

HCID 8778725317alpha-Ethinyl-11beta-fluoro-17beta-hydroxy-7alpha-methylestr-4-en-3-one

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 9.17 g of cerium(III) chloride in 60 ml of tetrahydrofuran was mixed drop by drop at 0° C. with 74.2 ml of an ethinylmagnesium bromide solution (0.5 M in tetrahydrofuran) and stirred for 1 hour at 0° C. Then, a solution of 2 g of crude 11β-fluoro-3-methoxy-7α-methylestra-3,5-dien-17-one in 40 ml of tetrahydrofuran was added drop by drop and stirred for another 3.5 hours at 0° C. For working-up, a saturated ammonium chloride solution was added, added to water, extracted three times with ethyl acetate, washed with semiconcentrated hydrochloric acid, sodium bicarbonate solution and sodium chloride solution, dried on sodium sulfate, concentrated by evaporation in a vacuum and chromatographed on silica gel with hexane/ethyl acetate. 1.15 g of pure 17α-ethinyl-11β-fluoro-17β-hydroxy-7α-methylestr-4-en-3-one with a melting point of 218-220° C. was obtained. [α]D=+19.2° (CHCl3).

Workup

  1. stirringstirred for another 3.5 hours at 0° C
  2. extractionextracted three times with ethyl acetate
  3. washwashed with semiconcentrated hydrochloric acid, sodium bicarbonate solution and sodium chloride solution
  4. customdried on sodium sulfate
  5. concentrationconcentrated by evaporation in a vacuum
  6. customchromatographed on silica gel with hexane/ethyl acetate

Sources & evidence

ORD record
ord-a068e470c15640649308e82e389c95f1
Source dataset
uspto-grants-2007_08
Patent number
US07262023B2

Reaction notes

Loading…