Pyridine → (1R,2R)-2-(4-Chloro-phenoxymethyl)-4-hydroxy-cyclopentanecarboxylic acid ethyl ester

HRID 1367488Notes

Reaction equation

HRID 1367488 reaction equation
[CH2:1]([O:3][C:4]([C@@H:6]1[CH2:10][CH:9]([O:11][Si](C(C)(C)C)(C)C)[CH2:8][C@H:7]1[CH2:19][O:20][C:21]1[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=1)=[O:5])[CH3:2].N1C=CC=CC=1.[Na]>O1CCCC1>[CH2:1]([O:3][C:4]([C@@H:6]1[CH2:10][CH:9]([OH:11])[CH2:8][C@H:7]1[CH2:19][O:20][C:21]1[CH:22]=[CH:23][C:24]([Cl:27])=[CH:25][CH:26]=1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 1049PyridineHCID 5360545Sodium2×HCID 66918824(1R,2R)-4-(tert-Butyl-dimethyl-silanyloxy)-2-(4-chloro-phenoxymethyl)-cyclopentanecarboxylic acid ethyl ester

Product 1

HCID 66919043(1R,2R)-2-(4-Chloro-phenoxymethyl)-4-hydroxy-cyclopentanecarboxylic acid ethyl esterYield 90.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a cold (ice bath) solution of (1R,2R)-4-(tert-Butyl-dimethyl-silanyloxy)-2-(4-chloro-phenoxymethyl)-cyclopentanecarboxylic acid ethyl ester (epimeric mixture, 529 mg) in tetrahydrofuran (20 mL) was slowly added pyridine (8.1 g) and a pyridine-hydrofluoric acid complex (70% HF w/w, 9.07 g). The mixture was stirred 3 h at room temperature then solid sodium hydrogenocarbonate an aqueous saturated solution of sodium hydrogenocarbonate were added to adjust the pH to 7. The mixture was extracted with dichloromethane and the combined organic layers were washed with an aqueous saturated solution of sodium hydrogenocarbonate, dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel with a gradient of cyclohexane/ethylacetate (6:1 to 1:1 v/v) as eluant to afford the title compound (0.346 g, 90%) as a light yellow oil. MS (EI): 299.1 (M+H)+.

Workup

  1. extractionThe mixture was extracted with dichloromethane
  2. washthe combined organic layers were washed with an aqueous saturated solution of sodium hydrogenocarbonate
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash chromatography on silica gel with a gradient of cyclohexane/ethylacetate (6:1 to 1:1 v/v) as eluant

Sources & evidence

ORD record
ord-e139cf2d3df64aab8347f5dd33265d36
Source dataset
uspto-grants-2011_02
Patent number
US07893099B2

Reaction notes

Loading…