(Diethylamino)sulfur trifluoride → N-{[1-(4-Fluoro-4-phenyl-cyclohexyl)-azetidin-3-ylcarbamoyl]-methyl}-3-trifluoromethyl-benzamide

HRID 1893323Notes

Reaction equation

HRID 1893323 reaction equation
O[C:2]1([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:7][CH2:6][CH:5]([N:8]2[CH2:11][CH:10]([NH:12][C:13]([CH2:15][NH:16][C:17](=[O:28])[C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[CH:19]=3)=[O:14])[CH2:9]2)[CH2:4][CH2:3]1.CCN(S(F)(F)[F:41])CC>C(Cl)Cl>[F:41][C:2]1([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:7][CH2:6][CH:5]([N:8]2[CH2:11][CH:10]([NH:12][C:13]([CH2:15][NH:16][C:17](=[O:28])[C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[CH:19]=3)=[O:14])[CH2:9]2)[CH2:4][CH2:3]1

Participants

4

Reactant 2

HCID 123472(Diethylamino)sulfur trifluorideHCID 46927116N-{[1-(4-Hydroxy-4-phenyl-cyclohexyl)-azetidin-3-ylcarbamoyl]-methyl}-3-trifluoromethyl-benzamide

Product 1

HCID 49763574N-{[1-(4-Fluoro-4-phenyl-cyclohexyl)-azetidin-3-ylcarbamoyl]-methyl}-3-trifluoromethyl-benzamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N-{[1-(4-Hydroxy-4-phenyl-cyclohexyl)-azetidin-3-ylcarbamoyl]-methyl}-3-trifluoromethyl-benzamide (as prepared in Example 30, 680 mg, 1.43 mmol) in DCM (5 mL) was treated with DAST (Aldrich, 418 μL, 4.29 mmol) dropwise at −78° C. for 4 hours. The reaction was quenched with MeOH, warmed to room temperature and partitioned between DCM and water. The organic layer was washed with brine, dried over anhydrous Na2SO4, filtered, concentrated and the residue was purified by a CombiFlash® system using ethyl acetate and 7N NH3 in MeOH as eluent (from pure ethyl acetate to 5% 7N NH3 in MeOH in ethyl acetate) to afford two title compound as white solid: less polar isomer.

Workup

  1. customThe reaction was quenched with MeOH
  2. custompartitioned between DCM and water
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customthe residue was purified by a CombiFlash® system

Sources & evidence

ORD record
ord-ccb7bfc4fb8549c8b282c5678eb4c9f6
Source dataset
uspto-grants-2013_08
Patent number
US08513229B2

Reaction notes

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