Oxalyl chloride → 2-cyclopentyl-N-[2-[2-[[3-(trifluoromethyl)-phenyl]sulfonyl]-ethylsulfanyl]-pyridin-3-yl]acetamide

HRID 888263Notes

Reaction equation

HRID 888263 reaction equation
C(Cl)(=O)C(Cl)=O.[CH:7]1([CH2:12][C:13]([OH:15])=O)[CH2:11][CH2:10][CH2:9][CH2:8]1.[F:16][C:17]([F:38])([F:37])[C:18]1[CH:19]=[C:20]([S:24]([CH2:27][CH2:28][S:29][C:30]2[C:35]([NH2:36])=[CH:34][CH:33]=[CH:32][N:31]=2)(=[O:26])=[O:25])[CH:21]=[CH:22][CH:23]=1.C([O-])(O)=O.[Na+]>C(Cl)Cl.O1CCOCC1.CCCCCC>[CH:7]1([CH2:12][C:13]([NH:36][C:35]2[C:30]([S:29][CH2:28][CH2:27][S:24]([C:20]3[CH:21]=[CH:22][CH:23]=[C:18]([C:17]([F:37])([F:38])[F:16])[CH:19]=3)(=[O:26])=[O:25])=[N:31][CH:32]=[CH:33][CH:34]=2)=[O:15])[CH2:8][CH2:9][CH2:10][CH2:11]1

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 71606Cyclopentylacetic acidHCID 516892Sodium BicarbonateHCID 67133713[2-[2-[[3-(Trifluoromethyl)phenyl]sulfonyl]-ethylsulfanyl]-pyridin-3-yl]amine

Product 1

HCID 469174392-cyclopentyl-N-[2-[2-[[3-(trifluoromethyl)-phenyl]sulfonyl]-ethylsulfanyl]-pyridin-3-yl]acetamideYield 54%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8058HexaneSolventHCID 312751,4-DioxaneSolvent

Procedure

254 μl (3.0 mmol) oxalylchloride were added to a solution of 192 mg (1.5 mmol) 2-cyclopentyl acetic acid in DCM (10 ml) and the mixture was stirred for 3 h at RT. Then the mixture was concentrated to small volume under vacuum and the residue was taken up with dioxane (6 ml). This solution was added at 0° C. to a solution of 362 mg (1.0 mmol) [2-[2-[[3-(trifluoromethyl)phenyl]sulfonyl]-ethylsulfanyl]-pyridin-3-yl]amine (VPF-001) in dioxane (5 ml). Then the reaction solution was mixed with 420 mg (5.0 mmol) NaHCO3 and stirred for 16 h at RT. Then the mixture was concentrated to small volume under vacuum and the residue was taken up with water. Then it was extracted with EE and the organic phase was washed with a saturated aqueous NaHCO3 solution and brine, dried over Na2SO4, filtered and concentrated to small volume under vacuum. Column chromatography (hexane/EE 3:1) of the residue yielded 231 mg (0.5 mmol, 54%) 2-cyclopentyl-N-[2-[2-[[3-(trifluoromethyl)-phenyl]sulfonyl]-ethylsulfanyl]-pyridin-3-yl]acetamide. MS: m/z 473.1 [M+H]+.

Workup

  1. concentrationThen the mixture was concentrated to small volume under vacuum
  2. stirringstirred for 16 h at RT
  3. concentrationThen the mixture was concentrated to small volume under vacuum
  4. extractionThen it was extracted with EE
  5. washthe organic phase was washed with a saturated aqueous NaHCO3 solution and brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated to small volume under vacuum

Sources & evidence

ORD record
ord-f3d7acdb66b34357b84229ab5fdef5cc
Source dataset
uspto-grants-2012_08
Patent number
US08247573B2

Reaction notes

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