Sodium Hydroxide → 3-(2-(4-Fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-4-methylbenzoic acid

HRID 1877659Notes

Reaction equation

HRID 1877659 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:20]=[CH:19][C:18]([C:21]4[CH:22]=[C:23]([CH:28]=[CH:29][C:30]=4[CH3:31])[C:24]([O:26]C)=[O:25])=[CH:17][C:11]=3[C:12]=2[C:13](=[O:16])[NH:14][CH3:15])=[CH:4][CH:3]=1.[OH-].[Na+]>CO.C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:20]=[CH:19][C:18]([C:21]4[CH:22]=[C:23]([CH:28]=[CH:29][C:30]=4[CH3:31])[C:24]([OH:26])=[O:25])=[CH:17][C:11]=3[C:12]=2[C:13](=[O:16])[NH:14][CH3:15])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 67292245HCID 67292245, compound

Product 1

HCID 592756533-(2-(4-Fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-4-methylbenzoic acid

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of methyl 3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-4-methylbenzoate (1 g, 2.4 mmol, 1 eq) in a 1:1 mixture of MeOH/THF at ambient temperature was added 5 eq. of NaOH and heated to 60° C. for 5 h. The mixture was cooled to ambient temperature and then in an ice-water bath, quenched slowly with 1.5 N HCl and then concentrated. The mixture with white precipitates was diluted with water and filtered to get the solid. It is further washed with water and dried in vacuum. Yield: 0.850 g (90%). This acid was also prepared by the coupling of 2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl trifluoromethanesulfonate with 4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acid (Cs2CO3, (Ph3)4Pd, H2O/1,4-dioxane (1:5), 90° C.) in a similar manner as described. 1H NMR (400 MHz, DMSO-d6): δ 2.32 (s, 3H), 2.82-2.83 (d, 3H, J=4.6 Hz), 7.36-7.48 (m, 6H), 7.56-7.57 (d, 1H, J=1.44 Hz), 7.75-7.77 (d, 1H, J=8.48 Hz), 7.81-8.03 (m, 2H), 8.46-8.48 (d, 1H, J=4.7 Hz), 12.92 (s, 1H). LCMS: (ES+) m/z=404.0 (M+H).

Workup

  1. temperatureThe mixture was cooled to ambient temperature
  2. customin an ice-water bath, quenched slowly with 1.5 N HCl
  3. concentrationconcentrated
  4. customThe mixture with white precipitates
  5. additionwas diluted with water
  6. filtrationfiltered
  7. customto get the solid
  8. washIt is further washed with water
  9. customdried in vacuum
  10. customThis acid was also prepared by the coupling of 2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl trifluoromethanesulfonate with 4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acid (Cs2CO3, (Ph3)4Pd, H2O/1,4-dioxane (1:5), 90° C.) in a similar manner

Sources & evidence

ORD record
ord-7a9c941275ca4669bc6ed8fa370dfcc9
Source dataset
uspto-grants-2012_11
Patent number
US08309558B2

Reaction notes

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