Sodium Hydroxide → 6-bromo-3-chloro-1-(1-methylethyl)-1H-indole-4-carboxylic acid

Temperature

55 °C

To a solution of methyl 6-bromo-3-chloro-1-(1-methylethyl)-1H-indole-4-carboxylate (1.2 g, 3.63 mmol) in THF (2.368 ml) and MeOH (14.21 ml) was added 3 N NaOH (1.573 ml, 4.72 mmol). The resulting mixture was heated at 55° C. for 4 h. The reaction was removed from the heat and the solvent removed in-vacuo. The remaining residue was dissolved with water (12 ml) and made acidic dropwise with 1 N HCl. The product precipitated and the slurry became too thick to stir and was diluted with water (10 ml). After the precipitation haulted no more acid was added. The solid was collected by vacuum filtration, washed with water, and air dried under vacuum overnight to give 6-bromo-3-chloro-1-(1-methylethyl)-1H-indole-4-carboxylic acid (650 mg, 2.033 mmol, 56.0% yield over 2 steps) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 13.22 (s, 1H), 8.09 (d, J=1.77 Hz, 1H), 7.89 (s, 1H), 7.45 (d, J=1.77 Hz, 1H), 4.88 (quin, J=6.63 Hz, 1H), 1.43 (d, J=6.57 Hz, 6H). MS (ES) [M+H]+ 316.0.

1. customThe reaction was removed from the
2. temperatureheat
3. customthe solvent removed in-vacuo
4. dissolutionThe remaining residue was dissolved with water (12 ml)
5. customThe product precipitated
6. additionwas diluted with water (10 ml)
7. customAfter the precipitation
8. additionwas added
9. filtrationThe solid was collected by vacuum filtration
10. washwashed with water, and air
11. customdried under vacuum overnight

ORD record

ord-c85355dc89e04eccb340bb3bbaa96274

Source dataset

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08536179B2