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

HRID 555161ノート

反応式

HRID 555161 の反応式
[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

参加物

4

反応物 2

HCID 14798Sodium HydroxideHCID 67292245HCID 67292245、化合物

生成物 1

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

試薬・触媒・溶媒 1

HCID 21899815MeOH tetrahydrofuran溶媒

反応条件

温度
60 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-dde8149499b84303b91e841e54683bab
出典データセット
uspto-grants-2011_11
特許番号
US08048887B2

反応ノート

読み込み中…