Diflunisal → Methyl 2',4'-difluoro-4-hydroxy-[1,1'-biphenyl]-3-carboxylate

HRID 242352Notes

Reaction equation

HRID 242352 reaction equation
[Si](C=[N+]=[N-])(C)(C)[CH3:2].[CH:8]1[C:13]([C:14]2[CH:15]=[CH:16][C:17]([F:21])=[CH:18][C:19]=2[F:20])=[CH:12][C:11]([C:22]([OH:24])=[O:23])=[C:10]([OH:25])[CH:9]=1>CO>[CH3:2][O:23][C:22]([C:11]1[CH:12]=[C:13]([C:14]2[CH:15]=[CH:16][C:17]([F:21])=[CH:18][C:19]=2[F:20])[CH:8]=[CH:9][C:10]=1[OH:25])=[O:24]

Participants

4

Reactant 2

HCID 3059DiflunisalHCID 167693Trimethylsilyldiazomethane

Product 1

HCID 491921Methyl 2',4'-difluoro-4-hydroxy-[1,1'-biphenyl]-3-carboxylateYield 71.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Compounds 32 and 33 were prepared according to Scheme 6. TMS-diazomethane (5.87 mL, 11.75 mmol, 2 M solution in hexane) was added to a solution of diflunisal (1.03 g, 4.11 mmol) in MeOH (10 mL) and stirred at rt for 5 h. Upon completion, the reaction was concentrated in vacuo and the residue was purified by flash chromatography (10:1 hexane:ethyl acetate) to afford 32 (774 mg, 71%) as a white solid. 1H NMR (CDCl3, 400 MHz) δ 7.97 (dd, 1H, J=2.2, 1.3 Hz), 7.59 (dt, 1H, J=8.8, 2.1 Hz), 7.36 (dq, 1H, J=7.7, 1.5 Hz), 7.48 (td, 1H, J=7.8, 1.7 Hz), 7.38 (dddd, 1H, J=8.8, 6.4 Hz), 7.05 (d, 1H, J=8.7 Hz), 6.93 (m, 1H), 6.90 (ddd, 1H, J=10.6, 8.9, 2.5 Hz), 3.96 (s, 3H). 13C NMR (CDCl3, 100 MHz) δ 170.6, 163.6, 161.3, 158.5, 136.4, 131.2, 130.3, 126.2, 124.2, 118.0, 112.6, 111.8, 104.6, 52.6, 124.2. HRFABMS calculated for C14H10F2O3 (M+) 264.0596, found 264.0598. Normal phase HPLC retention time: 6.9 min. Reverse phase HPLC retention time: 14.7 min. >99% pure.

Workup

  1. customCompounds 32 and 33 were prepared
  2. concentrationUpon completion, the reaction was concentrated in vacuo
  3. customthe residue was purified by flash chromatography (10:1 hexane:ethyl acetate)

Sources & evidence

ORD record
ord-dfcb3f9ca274432286e36ab3384126ee
Source dataset
uspto-grants-2014_02
Patent number
US08653119B2

Reaction notes

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