Water → HCID 23078339, compound

HRID 1259019Notes

Reaction equation

HRID 1259019 reaction equation
C1N=CN(C(N2C=NC=C2)=O)C=1.[CH:13]1[C:18]([C:19]2[CH:20]=[CH:21][C:22]([F:26])=[CH:23][C:24]=2[F:25])=[CH:17][C:16]([C:27]([OH:29])=[O:28])=[C:15]([OH:30])[CH:14]=1.[CH2:31](O)[CH2:32][CH3:33].O>CN(C=O)C>[F:25][C:24]1[CH:23]=[C:22]([F:26])[CH:21]=[CH:20][C:19]=1[C:18]1[CH:13]=[CH:14][C:15]([OH:30])=[C:16]([C:27]([O:29][CH2:31][CH2:32][CH3:33])=[O:28])[CH:17]=1

Participants

6

Reactant 4

HCID 962WaterHCID 10311-PropanolHCID 3059DiflunisalHCID 682631,1'-Carbonyldiimidazole

Product 1

HCID 23078339HCID 23078339, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

CDI (972 mg, 5.99 mmol) was added to a solution of diflunisal (1.50 g, 5.99 mmol) in DMF (30 mL). The reaction mixture was stirred at 50° C. for 2 h and n-PrOH (1.13 mL, 14.97 mmol) was dropwise added. The reaction mixture was stirred at 50° C. for 3 h and allowed to reach r.t. It was poured into H2O (50 mL) and extracted with Et2O (2×50 mL). The organic layer was washed with NaHCO3 (20 mL, saturated aqueous solution), dried over Na2SO4 (anhydrous), filtered and concentrated. The crude residue was flash chromatographed on SiO2 (2% EtOAc/hexanes) to furnish 1.33 g of propyl 2′,4′-difluoro-4-hydroxybiphenyl-3-carboxylate (yellow-coloured oil, yield: 76%).

Workup

  1. stirringThe reaction mixture was stirred at 50° C. for 3 h
  2. customto reach r.t
  3. extractionextracted with Et2O (2×50 mL)
  4. washThe organic layer was washed with NaHCO3 (20 mL, saturated aqueous solution)
  5. dry with materialdried over Na2SO4 (anhydrous)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customchromatographed on SiO2 (2% EtOAc/hexanes)

Sources & evidence

ORD record
ord-3ba0348a8fa74fcd800c40144864ec33
Source dataset
uspto-grants-2013_06
Patent number
US08466197B2

Reaction notes

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