Sodium Chlorite → 6-chloro-5-[4-(1-methylpyrrolidin-3-yl)phenyl]-1H-indole-3-carboxylic acid

Temperatur

0 °C

To a solution of 6-chloro-5-[4-(1-methylpyrrolidin-3-yl)phenyl]-1H-indole-3-carbaldehyde (crude, 0.23 g, 0.68 mmol) in acetonitrile (8 mL) and tert-butanol (8 mL) was added 2-methyl-2-butene (8 mL). The reaction mixture was cooled to 0° C. and treated with a solution of sodium chlorite (683 mg, 7.50 mmol) and sodium phosphate monobasic dihydrate (1.59 g, 10.2 mmol) in water (4 mL) dropwise. The reaction mixture was stirred at room temperature for two hours and treated with additional sodium chlorite (911 mg, 10.0 mmol) and sodium phosphate monobasic dihydrate (2.12 g, 13.6 mmol) in H2O (4 mL) and 2-methyl-2-butene (2 mL). The resulting mixture was stirred at room temperature for 16 h. The reaction mixture was evaporated in vacuo and the aqueous residue was extracted with EtOAc (3×30 mL). The combined organic layers were dried over Na2SO4 and concentrated in vacuo. The residue was purified via prep-HPLC to give 6-chloro-5-[4-(1-methylpyrrolidin-3-yl)phenyl]-1H-indole-3-carboxylic acid (10 mg) as a solid. MS (ES+) 354.9 (M+H)+. 1H NMR (400 MHz, CD3OD) δ 8.01 (m, 2 H), 7.59 (s, 1 H), 7.3-7.5 (m, 4 H), 3.40-4.00 (m, 5 H), 3.06 (s, 3 H), 2.1-2.7 (m, 2 H).

1. stirringThe resulting mixture was stirred at room temperature for 16 h
2. customThe reaction mixture was evaporated in vacuo
3. extractionthe aqueous residue was extracted with EtOAc (3×30 mL)
4. dry with materialThe combined organic layers were dried over Na2SO4
5. concentrationconcentrated in vacuo
6. customThe residue was purified via prep-HPLC

ORD-Eintrag

ord-581b03cb6d2346258a5c9c29ffe97eb4

Quelldatensatz

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09394285B2