Dimethyl Sulfoxide → 1-(S)-(1-(R)-(3,5-Bis(trifluoromethyl)phenyl)ethoxy)-2-(R)-(4-fluorophenyl)-3-(R)-(formyl)cyclopentane

HRID 1017765Notes

Reaction equation

HRID 1017765 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[F:11][C:12]([F:41])([F:40])[C:13]1[CH:14]=[C:15]([C@H:23]([O:25][C@H:26]2[CH2:30][CH2:29][C@@H:28]([CH2:31][OH:32])[C@@H:27]2[C:33]2[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=2)[CH3:24])[CH:16]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:18]=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[F:22][C:19]([F:20])([F:21])[C:17]1[CH:16]=[C:15]([C@H:23]([O:25][C@H:26]2[CH2:30][CH2:29][C@@H:28]([CH:31]=[O:32])[C@@H:27]2[C:33]2[CH:34]=[CH:35][C:36]([F:39])=[CH:37][CH:38]=2)[CH3:24])[CH:14]=[C:13]([C:12]([F:41])([F:11])[F:40])[CH:18]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 160877232alpha-(4-Fluorophenyl)-3beta-[[(R)-alpha-methyl-3,5-bis(trifluoromethyl)benzyl]oxy]cyclopentane-1beta-methanol

Product 1

HCID 228974301-(S)-(1-(R)-(3,5-Bis(trifluoromethyl)phenyl)ethoxy)-2-(R)-(4-fluorophenyl)-3-(R)-(formyl)cyclopentaneYield 86.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of 0.248 mL of oxalyl chloride in 8 mL of methylene chloride cooled to −70° C. was added dropwise 0.40 ml of DMSO. The reaction was stirred for 10-15 minutes and then a solution of 510 mg of 1-(S)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-2-(R)-(4-fluorophenyl)-3-(R)-(hydroxymethyl)-cyclopentane from Example 19, Method A or B in 5 mL of methylene chloride was added dropwise at −70° C. The reaction was stirred for 1 hour before dropwise addition of 2.0 mL of DIPEA in 3 mL of methylene chloride. After 5 minutes, the dry ice/acetone bath was removed and the reaction was allowed to warm to room temperature over 1 hour. The reaction was then diluted with methylene chloride and water containing 5 mL of 2N hydrochloric acid and the layers were separated. The aqueous layer was reextracted with methylene chloride and the organic layers were washed with brine, dried over sodium sulfate, combined and evaporated. The residue was purified by FC (10% ethyl acetate/hexanes) to give 440 mg of title compound as a waxy solid.

Workup

  1. waitAfter 5 minutes
  2. customthe dry ice/acetone bath was removed
  3. additionThe reaction was then diluted with methylene chloride and water containing 5 mL of 2N hydrochloric acid
  4. customthe layers were separated
  5. washthe organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. customevaporated
  8. customThe residue was purified by FC (10% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-0ff2243b252d4f738dcd22c74d5b8c7c
Source dataset
uspto-grants-2002_11
Patent number
US06479518B2

Reaction notes

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