Lithium iodide → 11beta-fluoro-3-hydroxy-7alpha-{5-[(2S)-2-(4-trifluoromethylphenylthiomethyl)-pyrrolidin-1-yl]-pentyl}-estra-1,3,5(10)-trien-17-one

HRID 650378Notes

Reaction equation

HRID 650378 reaction equation
Cl[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][C@@H:7]1[CH2:24][C:23]2[CH:22]=[C:21]([OH:25])[CH:20]=[CH:19][C:18]=2[C@@H:17]2[C@@H:8]1[C@H:9]1[C@@:13]([CH2:15][C@@H:16]2[F:26])([CH3:14])[C:12](=[O:27])[CH2:11][CH2:10]1.[F:28][C:29]([F:44])([F:43])[C:30]1[CH:35]=[CH:34][C:33]([S:36][CH2:37][C@@H:38]2[CH2:42][CH2:41][CH2:40][NH:39]2)=[CH:32][CH:31]=1.[I-].[Li+].C(=O)(O)[O-].[Na+]>CN(C)C=O>[F:26][C@H:16]1[CH2:15][C@@:13]2([CH3:14])[C@@H:9]([CH2:10][CH2:11][C:12]2=[O:27])[C@H:8]2[C@H:17]1[C:18]1[CH:19]=[CH:20][C:21]([OH:25])=[CH:22][C:23]=1[CH2:24][C@H:7]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][N:39]1[CH2:40][CH2:41][CH2:42][C@H:38]1[CH2:37][S:36][C:33]1[CH:34]=[CH:35][C:30]([C:29]([F:44])([F:28])[F:43])=[CH:31][CH:32]=1

Participants

6

Reactant 4

HCID 66321Lithium iodideHCID 516892Sodium BicarbonateHCID 57133071(2S)-2-(4-trifluoromethylphenylthiomethyl)-pyrrolidineHCID 68949346HCID 68949346, compound

Product 1

HCID 5727139511beta-fluoro-3-hydroxy-7alpha-{5-[(2S)-2-(4-trifluoromethylphenylthiomethyl)-pyrrolidin-1-yl]-pentyl}-estra-1,3,5(10)-trien-17-oneYield 57.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 0.5 g of 7α-(5-chloropentyl)-11β-fluoro-3-hydroxy-estra-1,3,5(10)-trien-17-one in 4 ml of dimethylformamide is stirred with 0.55 g of (2S)-2-(4-trifluoromethylphenylthiomethyl)-pyrrolidine and 0.32 g of lithium iodide for 2 hours at a bath temperature of 100° C. Then, it is added to sodium bicarbonate solution, extracted three times with ethyl acetate, washed with common salt solution, dried on sodium sulfate, concentrated by evaporation in a vacuum and chromatographed on silica gel with dichloromethaneiacetone. 0.45 g of 11β-fluoro-3-hydroxy-7α-{5-[(2S)-2-(4-trifluoromethylphenylthiomethyl)-pyrrolidin-1-yl]-pentyl}-estra-1,3,5(10)-trien-17-one with [α]D22+32.7° (c=0.51% in chloroform) is obtained.

Workup

  1. extractionextracted three times with ethyl acetate
  2. washwashed with common salt solution
  3. customdried on sodium sulfate
  4. concentrationconcentrated by evaporation in a vacuum
  5. customchromatographed on silica gel with dichloromethaneiacetone

Sources & evidence

ORD record
ord-16a9d6a9391b439b8a5e317779469ed1
Source dataset
uspto-grants-2001_08
Patent number
US06271403B1

Reaction notes

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