Potassium Carbonate → 3-Methanesulfonyl-N-methyl-N-{6-methyl-4-[2-(oxetan-3-ylmethoxy)-phenyl]-pyridin-3-yl}-5-trifluoromethyl-benzamide

HRID 878379Notes

Reaction equation

HRID 878379 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[C:12]([CH3:14])[N:11]=[CH:10][C:9]=1[N:15]([CH3:32])[C:16](=[O:31])[C:17]1[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[C:19]([S:27]([CH3:30])(=[O:29])=[O:28])[CH:18]=1.C([O-])([O-])=O.[K+].[K+].CC1C=CC(S(O[CH2:50][CH:51]2[CH2:54][O:53][CH2:52]2)(=O)=O)=CC=1.C([O-])(O)=O.[Na+]>CN(C=O)C.CCOC(C)=O>[CH3:30][S:27]([C:19]1[CH:18]=[C:17]([CH:22]=[C:21]([C:23]([F:25])([F:26])[F:24])[CH:20]=1)[C:16]([N:15]([CH3:32])[C:9]1[CH:10]=[N:11][C:12]([CH3:14])=[CH:13][C:8]=1[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[O:1][CH2:50][CH:51]1[CH2:54][O:53][CH2:52]1)=[O:31])(=[O:29])=[O:28]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 86670828Oxetan-3-ylmethyl 4-methylbenzene-1-sulfonateHCID 136414059N-(4-(2-hydroxyphenyl)-6-methylpyridin-3-yl)-N-methyl-3-(methylsulfonyl)-5-(trifluoromethyl)benzamide

Product 1

HCID 706633453-Methanesulfonyl-N-methyl-N-{6-methyl-4-[2-(oxetan-3-ylmethoxy)-phenyl]-pyridin-3-yl}-5-trifluoromethyl-benzamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution N-(4-(2-hydroxyphenyl)-6-methylpyridin-3-yl)-N-methyl-3-(methylsulfonyl)-5-(trifluoromethyl)benzamide (100 mg, 215 μmol, example 318, intermediate a) in DMF (2 ml) was added K2CO3 (59.5 mg, 431 μmol) and oxetan-3-ylmethyl 4-methylbenzenesulfonate (57.4 mg, 237 μmol). The reaction mixture was stirred for 2 hours at room temperature and for 18 hours at 80° C. The reaction mixture was poured on 30 mL 10% aqueous NaHCO3 solution and 30 mL EtOAc and the layers were separated. The aqueous layer was extracted a second time with 30 mL EtOAc. The organic layers were washed with 30 mL brine, dried over MgSO4, filtered and concentrated under vacuum. The compound was purified by silica gel chromatography on a 10 g column using an MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:EtOAc (100:0 to 0:100). Colorless solid (87 mg, 76%). MS (ESI): m/z=535.150 [M+H]+.

Workup

  1. customthe layers were separated
  2. extractionThe aqueous layer was extracted a second time with 30 mL EtOAc
  3. washThe organic layers were washed with 30 mL brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  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)

Sources & evidence

ORD record
ord-fbbaf037139f486c86e585d0be978996
Source dataset
uspto-grants-2015_03
Patent number
US08987307B2

Reaction notes

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