Methanol → 3-(4',5'-Difluoro-2'-methoxybiphenyl-4-yloxymethyl)-4-fluorobenzoic acid

HRID 1665242Notes

Reaction equation

HRID 1665242 reaction equation
C[O:2][C:3](=[O:29])[C:4]1[CH:9]=[CH:8][C:7]([F:10])=[C:6]([CH2:11][O:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]3[CH:24]=[C:23]([F:25])[C:22]([F:26])=[CH:21][C:20]=3[O:27][CH3:28])=[CH:15][CH:14]=2)[CH:5]=1.[OH-].[Li+].CO>C1COCC1>[F:26][C:22]1[C:23]([F:25])=[CH:24][C:19]([C:16]2[CH:15]=[CH:14][C:13]([O:12][CH2:11][C:6]3[CH:5]=[C:4]([CH:9]=[CH:8][C:7]=3[F:10])[C:3]([OH:29])=[O:2])=[CH:18][CH:17]=2)=[C:20]([O:27][CH3:28])[CH:21]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 3939Lithium HydroxideHCID 671503573-(4',5'-Difluoro-2'-methoxybiphenyl-4-yloxymethyl)-4-fluorobenzoic acid methyl ester

Product 1

HCID 582711923-(4',5'-Difluoro-2'-methoxybiphenyl-4-yloxymethyl)-4-fluorobenzoic acidYield 96%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

3-(4′,5′-Difluoro-2′-methoxybiphenyl-4-yloxymethyl)-4-fluorobenzoic acid methyl ester (0.76 g, 1.9 mmol) was dissolved in THF (10 mL) and lithium hydroxide solution (0.5N, 8 mL) was added followed by addition of methanol (2 mL). The mixture was refluxed for 2 hrs and solvents were evaporated. The mixture was extracted with ether and water. The aqueous layer was treated with hydrochloric acid (1N, 5 mL) and extracted with ethyl acetate. The organic layer was washed with brine and dried over sodium sulfate. Solvents were evaporated to give a white solid as 3-(4′,5′-difluoro-2′-methoxybiphenyl-4-yloxymethyl)-4-fluorobenzoic acid (0.7 g, 96%). HRMS-ES calculated for C21, H15, F3, O4, 411.0814; found m/z 411.0815 [M+Na]+; 1H-NMR (DMSO-d6) δ ppm 13.15 (br, s, 1H), 8.16 (dd, J=7.2, 1.8 Hz, 1H), 7.96-8.04 (m, 1H), 7.32-7.45 (m, 4H), 7.24 (dd, J=13.0, 6.9 Hz, 1H), 7.08 (d, J=8.5 Hz, 2H), 5.24 (s, 2H), 3.76 (s, 3H).

Workup

  1. temperatureThe mixture was refluxed for 2 hrs
  2. customsolvents were evaporated
  3. extractionThe mixture was extracted with ether and water
  4. additionThe aqueous layer was treated with hydrochloric acid (1N, 5 mL)
  5. extractionextracted with ethyl acetate
  6. washThe organic layer was washed with brine
  7. dry with materialdried over sodium sulfate
  8. customSolvents were evaporated

Sources & evidence

ORD record
ord-4f3160223af74e5293c39414553a34e1
Source dataset
uspto-grants-2011_10
Patent number
US08039495B2

Reaction notes

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