Ethyl Acetate → US10385022, Example 314

HRID 878370Notes

Reaction equation

HRID 878370 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([CH3:14])[N:11]=[CH:10][C:9]=2[N:15]([CH3:33])[C:16](=[O:32])[C:17]2[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[C:19](SC3COC3)[CH:18]=2)=[C:4]([O:34][CH3:35])[CH:3]=1.O[O:37][S:38]([O-:40])=O.[K+].[O-]S([O-])(=S)=O.[Na+].[Na+].C[CH2:50][O:51][C:52]([CH3:54])=O>CO.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([CH3:14])[N:11]=[CH:10][C:9]=2[N:15]([CH3:33])[C:16](=[O:32])[C:17]2[CH:22]=[C:21]([C:23]([F:25])([F:24])[F:26])[CH:20]=[C:19]([S:38]([CH:54]3[CH2:50][O:51][CH2:52]3)(=[O:40])=[O:37])[CH:18]=2)=[C:4]([O:34][CH3:35])[CH:3]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 24477Sodium ThiosulfateHCID 23707502Potassium hydroxy sulfiteHCID 70663579N-[4-(4-Fluoro-2-methoxy-phenyl)-6-methyl-pyridin-3-yl]-N-methyl-3-(oxetan-3-ylsulfanyl)-5-trifluoromethyl-benzamide

Product 1

HCID 70663309US10385022, Example 314

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To an ice-cold solution of N-(4-(4-fluoro-2-methoxyphenyl)-6-methylpyridin-3-yl)-N-methyl-3-(oxetan-3-ylthio)-5-(trifluoromethyl)benzamide (0.045 g, 88.8 μmol, example 310) in MeOH (2 mL) and water (0.5 mL) was added Oxone® (137 mg, 222 μmol) and stirring was continued at room temperature for 2.5 hours. The reaction mixture was poured on 10% aqueous Na2S2O3 solution and EtOAc and the layers were separated. The aqueous layer was saturated with sodium chloride, extracted three times with EtOAc. The organic layers were washed once with brine, dried over MgSO4, filtered and evaporated. The compound was purified by silica gel chromatography on a 10 g column using an MPLC (ISCO) system eluting with a gradient of n-heptane:EtOAc (100:0 to 0:100). The product was purified by preparative HPLC (Gemini NX column) using a gradient of MeOH:water (containing 0.1% formic acid) (20:80 to 98:2). Light brown foam (0.038 g; 79%). MS (ESI): m/z=539.13 [M+H]+.

Workup

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

Sources & evidence

ORD record
ord-94294e1cfc494c548162e5eaba7bbae1
Source dataset
uspto-grants-2015_03
Patent number
US08987307B2

Reaction notes

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