Potassium Carbonate → HCID 70663375, compound

HRID 878316Notes

Reaction equation

HRID 878316 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][N:11]=[CH:10][C:9]=1[N:14]([CH3:31])[C:15](=[O:30])[C:16]1[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[C:18]([S:26]([CH3:29])(=[O:28])=[O:27])[CH:17]=1.C([O-])([O-])=O.[K+].[K+].[CH:38]1(Br)[CH2:41][CH2:40][CH2:39]1.C([O-])(O)=O.[Na+]>CN(C=O)C.CCOC(C)=O>[CH:38]1([O:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=2[C:8]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[N:14]([CH3:31])[C:15](=[O:30])[C:16]2[CH:21]=[C:20]([C:22]([F:24])([F:25])[F:23])[CH:19]=[C:18]([S:26]([CH3:29])(=[O:28])=[O:27])[CH:17]=2)[CH2:41][CH2:40][CH2:39]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 78110BromocyclobutaneHCID 516892Sodium BicarbonateHCID 136414058HCID 136414058, compound

Product 1

HCID 70663375HCID 70663375, compoundYield 35%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution N-(4-(2-hydroxyphenyl)pyridin-3-yl)-N-methyl-3-(methylsulfonyl)-5-(trifluoromethyl)benzamide (100 mg, 222 μmol, example 263, intermediate a) in DMF (2 mL) was added K2CO3 (61.4 mg, 444 μmol) and cyclobutylbromide (33.0 mg, 244 μmol). The reaction mixture was stirred for 2 hours at room temperature. The reaction mixture was stirred 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 20 g column using an MPLC (Flashmaster) system eluting with a gradient of n-heptane:EtOAc (100:0 to 0:100). A second purification step using preparative HPLC (Gemini NX column) with a gradient of MeOH:water (containing 0.05% formic acid) (80:20 to 98:2) furnished the desired compound as a colorless foam (39 mg, 35%). MS (ESI): m/z=505.141 [M+H]+.

Workup

  1. stirringThe reaction mixture was stirred for 18 hours at 80° C
  2. customthe layers were separated
  3. extractionThe aqueous layer was extracted a second time with 30 mL EtOAc
  4. washThe organic layers were washed with 30 mL brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe compound was purified by silica gel chromatography on a 20 g column
  9. washeluting with a gradient of n-heptane:EtOAc (100:0 to 0:100)
  10. customA second purification step

Sources & evidence

ORD record
ord-641d79a4d16e4235aa844dece8734008
Source dataset
uspto-grants-2015_03
Patent number
US08987307B2

Reaction notes

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