Water → 2-Fluoro-4-{5-[2-(methoxymethyl)-2'-methylbiphenyl-4-yl]-1,2,4-oxadiazol-3-yl}benzoic acid

HRID 219917Notes

Reaction equation

HRID 219917 reaction equation
[F:1][C:2]1[CH:11]=[C:10]([C:12]2[N:16]=[C:15]([C:17]3[CH:22]=[CH:21][C:20]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=4[CH3:29])=[C:19]([CH2:30][O:31][CH3:32])[CH:18]=3)[O:14][N:13]=2)[CH:9]=[CH:8][C:3]=1[C:4]([O:6]C)=[O:5].[OH-].[Na+].O>C1COCC1.CO>[F:1][C:2]1[CH:11]=[C:10]([C:12]2[N:16]=[C:15]([C:17]3[CH:22]=[CH:21][C:20]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=4[CH3:29])=[C:19]([CH2:30][O:31][CH3:32])[CH:18]=3)[O:14][N:13]=2)[CH:9]=[CH:8][C:3]=1[C:4]([OH:6])=[O:5]

Participants

6

Reactant 3

HCID 962WaterHCID 14798Sodium HydroxideHCID 66678608Methyl 2-fluoro-4-{5-[2-(methoxymethyl)-2'-methylbiphenyl-4-yl]-1,2,4-oxadiazol-3-yl}benzoate

Product 1

HCID 252563812-Fluoro-4-{5-[2-(methoxymethyl)-2'-methylbiphenyl-4-yl]-1,2,4-oxadiazol-3-yl}benzoic acidYield 75.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of methyl 2-fluoro-4-{5-[2-(methoxymethyl)-2′-methylbiphenyl-4-yl]-1,2,4-oxadiazol-3-yl}benzoate (16 g; 37 mmol) in THF (400 mL) and MeOH (400 mL) at RT was treated with NaOH (37 mL; 5 M; 184.99 mmol). The reaction mixture was stirred at RT for 12 hours. The reaction mixture was concentrated to give a yellow solid. Water (600 mL) was added and the aqueous phase was washed with EtOAc (250 mL). Then the aqueous phase was acidified with HCl cc until pH 2 and extracted with EtOAc (2×300 mL). Organics were washed with brine, dried over MgSO4 and concentrated affording the title compound as a beige solid (11.66 g, 75%). 1H NMR (DMSO, 400 MHz) δ 13.64 (br s, 1H), 8.33 (d, J=1.41 Hz, 1H), 8.17 (dd, J=7.92 Hz, 1.4 Hz, 1H), 8.13-8.03 (m, 2H), 7.96 (dd, J=11.10 Hz, 1.17 HZ, 1H), 7.43 (d, J=7.91 Hz, 1H), 7.37-7.27 (m, 3H), 7.15 (d, J=7.03 Hz, 1H), 4.25-4.14 (m, 2H), 3.25 (s, 3H), 2.04 (s, 3H). LC/MS (Method B): 419.1 (M+H)+; 417.2 (M−H)−. HPLC: Rt 5.19 min (Purity: 99.2%).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customto give a yellow solid
  3. washthe aqueous phase was washed with EtOAc (250 mL)
  4. extractionextracted with EtOAc (2×300 mL)
  5. washOrganics were washed with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-29574812984b48a2baaa6759e3657191
Source dataset
uspto-grants-2012_06
Patent number
US08202865B2

Reaction notes

Loading…