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

HRID 555161Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 555161
[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

Komponenten

4

Edukt 2

HCID 14798Sodium HydroxideHCID 67292245HCID 67292245, Verbindung

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 21899815MeOH tetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-dde8149499b84303b91e841e54683bab
Quelldatensatz
uspto-grants-2011_11
Patentnummer
US08048887B2

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