Sodium Iodide → (1R,2R,4S)-4-(tert-Butyl-dimethyl-silanyloxy)-2-[4-(4-fluoro-phenyl)-piperidin-1-ylmethyl]-cyclopentanecarboxylic acid ethyl ester

HRID 1367543Notes

Reaction equation

HRID 1367543 reaction equation
[CH2:1]([O:3][C:4]([C@@H:6]1[CH2:10][CH:9]([O:11][Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13])[CH2:8][C@H:7]1[CH2:19]OS(C1C=CC(C)=CC=1)(=O)=O)=[O:5])[CH3:2].[F:31][C:32]1[CH:37]=[CH:36][C:35]([CH:38]2[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]2)=[CH:34][CH:33]=1.[I-].[Na+].C(N(CC)CC)C>CN(C)C=O>[CH2:1]([O:3][C:4]([C@@H:6]1[CH2:10][C@@H:9]([O:11][Si:12]([C:15]([CH3:16])([CH3:17])[CH3:18])([CH3:14])[CH3:13])[CH2:8][C@H:7]1[CH2:19][N:41]1[CH2:42][CH2:43][CH:38]([C:35]2[CH:34]=[CH:33][C:32]([F:31])=[CH:37][CH:36]=2)[CH2:39][CH2:40]1)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 8471TriethylamineHCID 27591364-(4-Fluorophenyl)piperidineHCID 86649030(1R,2R)-4-(tert-Butyl-dimethyl-silanyloxy)-2-(toluene-4-sulfonyloxymethyl)-cyclopentanecarboxylic acid ethyl ester

Product 1

HCID 66918951(1R,2R,4S)-4-(tert-Butyl-dimethyl-silanyloxy)-2-[4-(4-fluoro-phenyl)-piperidin-1-ylmethyl]-cyclopentanecarboxylic acid ethyl esterYield 41%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of (1R,2R)-4-(tert-Butyl-dimethyl-silanyloxy)-2-(toluene-4-sulfonyloxymethyl)-cyclopentanecarboxylic acid ethyl ester (example 148, step 1, epimeric mixture, 410 mg), 4-(4-Fluoro-phenyl)-piperidine (cas # 6716-98-9, 291 mg), sodium iodide (1.36 g) and triethylamine (545 mg) in N,N-dimethylformamide (2.8 mL) was stirred at 90° C. over 6 h. The reaction mixture was partitioned between ethyl acetate and an aqueous saturated solution of sodium hydrogenocarbonate. The aqueous layer was extracted with ethyl acetate and the combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica gel with a gradient of cyclohexane/ethyl acetate (9:1 to 1:1 v/v) as eluant to afford the title compound (170 mg, 41%) as a yellow liquid. MS (EI): 464.4 (M+H)+.

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate
  2. extractionThe aqueous layer was extracted with ethyl acetate
  3. dry with materialthe combined organic layers were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash chromatography on silica gel with a gradient of cyclohexane/ethyl acetate (9:1 to 1:1 v/v) as eluant

Sources & evidence

ORD record
ord-ef2dabc918964390ba7163f2db9c7f55
Source dataset
uspto-grants-2011_02
Patent number
US07893099B2

Reaction notes

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