Diflunisal → HCID 69619823, compound

HRID 1259025Notes

Reaction equation

HRID 1259025 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.C(O)(C)(C)C.[CH2:36]1[CH2:46]CN2C(=NCCC2)[CH2:38][CH2:37]1.C([O-])(O)=O.[Na+]>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][CH2:46][CH2:36][CH2:37][CH3:38])=[O:28])[CH:17]=1

Participants

7

Reactant 5

HCID 3059DiflunisalHCID 6386tert-ButanolHCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 516892Sodium Bicarbonate

Product 1

HCID 69619823HCID 69619823, compoundYield 68%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

CDI (1.29 g, 7.99 mmol) was added to a solution of diflunisal (2.02 g, 8.07 mmol) in DMF (20 mL). The reaction mixture was stirred at 50° C. for 30 min and tert-butyl alcohol (1.50 mL, 14.97 mmol) and DBU (2.40 mL, 16.064 mmol) were dropwise added. The reaction mixture was stirred at 50° C. for 20 h and allowed to reach r.t. It was poured into NaHCO3 (100 mL, saturated aqueous solution) and extracted with EtOAc (100 mL). The organic layer was dried over Na2SO4 (anhydrous), filtered and concentrated. The crude residue was flash chromatographed on SiO2 (5% EtOAc/hexanes) to furnish 1.677 g of ten-butyl 2′,4′-difluoro-4-hydroxybiphenyl-3-carboxylate (colourless oil, yield: 68%).

Workup

  1. stirringThe reaction mixture was stirred at 50° C. for 20 h
  2. customto reach r.t
  3. extractionextracted with EtOAc (100 mL)
  4. dry with materialThe organic layer was dried over Na2SO4 (anhydrous)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customchromatographed on SiO2 (5% EtOAc/hexanes)

Sources & evidence

ORD record
ord-4b7afbe68d7844ba8f764546786f63e5
Source dataset
uspto-grants-2013_06
Patent number
US08466197B2

Reaction notes

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