Citric Acid → N-[4-(5-Fluoro-2-methyl-phenyl)-6-methyl-pyridin-3-yl]-3-methanesulfonyl-N-methyl-5-trifluoromethyl-benzamide

HRID 878303Notes

Reaction equation

HRID 878303 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([N:8]([CH3:25])[C:9](=[O:24])[C:10]2[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[C:12]([S:20]([CH3:23])(=[O:22])=[O:21])[CH:11]=2)=[C:4]([C:26]2[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:27]=2[CH3:33])[CH:3]=1.[Cl-].C[Zn+].[CH3:37]N1CCN(C)C1=O.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1.CCOC(C)=O>[F:32][C:30]1[CH:29]=[CH:28][C:27]([CH3:33])=[C:26]([C:4]2[CH:3]=[C:2]([CH3:37])[N:7]=[CH:6][C:5]=2[N:8]([CH3:25])[C:9](=[O:24])[C:10]2[CH:15]=[C:14]([C:16]([F:19])([F:17])[F:18])[CH:13]=[C:12]([S:20]([CH3:23])(=[O:21])=[O:22])[CH:11]=2)[CH:31]=1

Participants

7

Reactant 4

HCID 311Citric AcidHCID 66611,3-Dimethyl-2-imidazolidinoneHCID 86670811HCID 86670811, compoundHCID 178477797HCID 178477797, compound

Product 1

HCID 70663247N-[4-(5-Fluoro-2-methyl-phenyl)-6-methyl-pyridin-3-yl]-3-methanesulfonyl-N-methyl-5-trifluoromethyl-benzamide

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of N-(6-chloro-4-(5-fluoro-2-methylphenyl)pyridin-3-yl)-N-methyl-3-(methylsulfonyl)-5-(trifluoromethyl)benzamide (0.055 g, 110 μmol, example 253) in THF (1.5 mL) were added methylzinc(II) chloride (82.4 μL, 165 μmol), 1,3-dimethyl-2-imidazolidinone (DMI) (0.3 mL) and PEPPSI-IPr (1.49 mg, 2.2 μmol, CAS RN 905459-27-0) and the clear solution was stirred at 50° C. for 2 hours. The reaction mixture was poured on 10% aqueous citric acid solution and EtOAc and the layers were separated. The aqueous layer was extracted twice with EtOAc. The organic layers were washed once with brine, dried over MgSO4, filtered, treated with silica gel and evaporated. The compound was purified by silica gel chromatography on a 5 g column using an MPLC system eluting with a gradient of n-heptane:EtOAc (100:0 to 100:100). The product was purified by preparative HPLC (Gemini NX column) using a gradient of MeOH:water (containing 0.05% triethylamine) (20:80 to 98:2). Colorless foam (0.022 g; 41%). MS (ESI): m/z=481.12 [M+H]+.

Workup

  1. customthe layers were separated
  2. extractionThe aqueous layer was extracted twice with EtOAc
  3. washThe organic layers were washed once with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. additiontreated with silica gel
  7. customevaporated
  8. customThe compound was purified by silica gel chromatography on a 5 g column
  9. washeluting with a gradient of n-heptane:EtOAc (100:0 to 100:100)
  10. customThe product was purified by preparative HPLC (Gemini NX column)

Sources & evidence

ORD record
ord-a199d0dd5b324b379fb204f5bb349b4d
Source dataset
uspto-grants-2015_03
Patent number
US08987307B2

Reaction notes

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