Potassium Carbonate → 3-hydroxy-5-[(1R)-2-hydroxy-1-methylethoxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide

HRID 20575Notes

Reaction equation

HRID 20575 reaction equation
I[Si](C)(C)C.[OH:6][C:7]1[CH:8]=[C:9]([CH:19]=[C:20]([O:22][C@H:23]([CH3:27])[CH2:24][O:25]C)[CH:21]=1)[C:10]([NH:12][C:13]1[CH:17]=[CH:16][N:15]([CH3:18])[N:14]=1)=[O:11].C(=O)([O-])[O-].[K+].[K+].S([O-])([O-])(=O)=S.[Na+].[Na+]>C(#N)C.CO>[OH:6][C:7]1[CH:8]=[C:9]([CH:19]=[C:20]([O:22][C@H:23]([CH3:27])[CH2:24][OH:25])[CH:21]=1)[C:10]([NH:12][C:13]1[CH:17]=[CH:16][N:15]([CH3:18])[N:14]=1)=[O:11]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 24477Sodium ThiosulfateHCID 85247Trimethylsilyl iodideHCID 593469263-hydroxy-5-[(1R)-2-methoxy-1-methylethoxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide

Product 1

HCID 593468763-hydroxy-5-[(1R)-2-hydroxy-1-methylethoxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamideYield 64%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent

Procedure

Iodotrimethylsilane (6.64 mL, 47 mmol) was added to a solution of 3-hydroxy-5-[(1R)-2-methoxy-1-methylethoxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide (2.86 g, 9.38 mmol) in acetonitrile (120 mL) and the resultant mixture stirred for 24 hours. Methanol (30 mL) was added and the mixture stirred for 30 minutes, saturated potassium carbonate (30 mL) and saturated sodium thiosulphate (30 mL) were then added and the mixture stirred for 20 mins. The acetonitrile was removed in vacuo and water (50 mL) added. The mixture was adjusted to pH4 with 1M hydrochloric acid, extracted into ethyl acetate (3×100 mL) and the combined extracts washed with brine (50 mL), dried (MgSO4) and evaporated to a residue which was chromatographed on silica, eluting with a gradient of 0-50% methanol in ethyl acetate, to give the desired compound (1.75 g).

Workup

  1. stirringthe mixture stirred for 20 mins
  2. customThe acetonitrile was removed in vacuo and water (50 mL)
  3. additionadded
  4. extractionextracted into ethyl acetate (3×100 mL)
  5. washthe combined extracts washed with brine (50 mL)
  6. dry with materialdried (MgSO4)
  7. customevaporated to a residue which
  8. customwas chromatographed on silica
  9. washeluting with a gradient of 0-50% methanol in ethyl acetate

Sources & evidence

ORD record
ord-c915cfb25161492b96e2997f6cc8dfc9
Source dataset
uspto-grants-2010_06
Patent number
US07745475B2

Reaction notes

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