Water → 3-[5-Chloro-2-fluoro-4-(methylsulfonyl)phenoxy]-5-[(1S)-2-hydroxy-1-methylethoxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide

HRID 20551Notes

Reaction equation

HRID 20551 reaction equation
C(=O)([O-])[O-].[K+].[K+].[OH:7][C:8]1[CH:9]=[C:10]([CH:20]=[C:21]([O:23][C@@H:24]([CH3:27])[CH2:25][OH:26])[CH:22]=1)[C:11]([NH:13][C:14]1[CH:18]=[CH:17][N:16]([CH3:19])[N:15]=1)=[O:12].[Cl:28][C:29]1[CH:34]=[C:33](F)[C:32]([F:36])=[CH:31][C:30]=1[S:37]([CH3:40])(=[O:39])=[O:38].O>CN1C(=O)CCC1>[Cl:28][C:29]1[C:30]([S:37]([CH3:40])(=[O:39])=[O:38])=[CH:31][C:32]([F:36])=[C:33]([CH:34]=1)[O:7][C:8]1[CH:9]=[C:10]([CH:20]=[C:21]([O:23][C@@H:24]([CH3:27])[CH2:25][OH:26])[CH:22]=1)[C:11]([NH:13][C:14]1[CH:18]=[CH:17][N:16]([CH3:19])[N:15]=1)=[O:12]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 593468611-Chloro-4,5-difluoro-2-(methylsulfonyl)benzeneHCID 593468923-Hydroxy-5-{[(S)-2-hydroxy-1-methylethyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide

Product 1

HCID 116562293-[5-Chloro-2-fluoro-4-(methylsulfonyl)phenoxy]-5-[(1S)-2-hydroxy-1-methylethoxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamideYield 49.5%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
115 °C

Procedure

Potassium carbonate (1.00 g) was added to a solution of 3-hydroxy-5-{[(1S)-2-hydroxy-1-methylethyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide (1.41 g) and 1-chloro-4,5-difluoro-2-(methylsulfonyl)benzene (0.79 g) in NMP (20 mL). The mixture was heated to 115° C. for 3.5 hours and left to cool before being poured into water (300 mL) and extracted with ethyl acetate (2×150 mL). The combined organics were washed with water, brine and dried (MgSO4) before evaporation in vacuo. Chromatography on silica, eluting with 0 to 10% methanol in ethyl acetate, afforded the desired compound (0.86 g)

Workup

  1. waitleft
  2. temperatureto cool
  3. extractionextracted with ethyl acetate (2×150 mL)
  4. washThe combined organics were washed with water, brine
  5. dry with materialdried (MgSO4)
  6. custombefore evaporation in vacuo
  7. washChromatography on silica, eluting with 0 to 10% methanol in ethyl acetate

Sources & evidence

ORD record
ord-f8b4f31d8622478d8f0ecddec23a3da2
Source dataset
uspto-grants-2010_06
Patent number
US07745475B2

Reaction notes

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