Sodium Hydroxide → N-[4-(4-Fluoro-2-methoxy-phenyl)-pyridin-3-yl]-3-methanesulfonyl-N-methyl-5-trifluoromethoxy-benzamide

HRID 878287Notes

Reaction equation

HRID 878287 reaction equation
N1CCC[C@H]1C(O)=O.[OH-].[Na+].Br[C:12]1[CH:13]=[C:14]([CH:34]=[C:35]([O:37][C:38]([F:41])([F:40])[F:39])[CH:36]=1)[C:15]([N:17]([C:19]1[CH:20]=[N:21][CH:22]=[CH:23][C:24]=1[C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:26]=1[O:32][CH3:33])[CH3:18])=[O:16].[CH3:42][S:43]([O-:45])=[O:44].[Na+].[NH4+].[Cl-]>CS(C)=O.[Cu]I.CCOC(C)=O>[F:31][C:28]1[CH:29]=[CH:30][C:25]([C:24]2[CH:23]=[CH:22][N:21]=[CH:20][C:19]=2[N:17]([CH3:18])[C:15](=[O:16])[C:14]2[CH:34]=[C:35]([O:37][C:38]([F:41])([F:40])[F:39])[CH:36]=[C:12]([S:43]([CH3:42])(=[O:45])=[O:44])[CH:13]=2)=[C:26]([O:32][CH3:33])[CH:27]=1

Participants

9

Reactant 5

HCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 145742L-ProlineHCID 2733271Sodium methanesulfinateHCID 706632413-Bromo-N-[4-(4-fluoro-2-methoxy-phenyl)-pyridin-3-yl]-N-methyl-5-trifluoromethoxy-benzamide

Product 1

HCID 60196595N-[4-(4-Fluoro-2-methoxy-phenyl)-pyridin-3-yl]-3-methanesulfonyl-N-methyl-5-trifluoromethoxy-benzamide

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of L-proline (18.4 mg, 160 μmol) in DMSO (2 mL) was added sodium hydroxide (6.41 mg, 160 μmol) and the turbid mixture was stirred at room temperature for 30 minutes. This mixture was added to 3-bromo-N-[4-(4-fluoro-2-methoxy-phenyl)-pyridin-3-yl]-N-methyl-5-trifluoromethoxy-benzamide (0.1 g, 200 μmol) and the resulting suspension was treated with copper(I)iodide (30.5 mg, 160 μmol) and sodium methanesulfinate (164 mg, 1.6 mmol). The reaction mixture was heated to 120° C. for 19 hours. After cooling down to room temperature the reaction mixture was poured on saturated aqueous NH4Cl solution and EtOAc and the layers were separated. The aqueous layer was extracted twice with EtOAc. The organic layers were washed with brine, dried over MgSO4, filtered, treated with silica gel and evaporated. The compound was purified by silica gel chromatography on a 10 g column using an MPLC system eluting with a gradient of n-heptane:EtOAc (100:0 to 0:100). Colorless foam (0.065 g; 65%). MS (ESI): m/z=499.09 [M+H]+.

Workup

  1. temperatureThe reaction mixture was heated to 120° C. for 19 hours
  2. temperatureAfter cooling down to room temperature the reaction mixture
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted twice with EtOAc
  5. washThe organic layers were washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. additiontreated with silica gel
  9. customevaporated
  10. customThe compound was purified by silica gel chromatography on a 10 g column
  11. washeluting with a gradient of n-heptane:EtOAc (100:0 to 0:100)

Sources & evidence

ORD record
ord-884f6567c8144066913e1c1509b68869
Source dataset
uspto-grants-2015_03
Patent number
US08987307B2

Reaction notes

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