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ChemicalBook CAS DataBase List 6-FLUORO-1H-INDOLE-3-CARBOXYLIC ACID
23077-44-3

6-FLUORO-1H-INDOLE-3-CARBOXYLIC ACID synthesis

5synthesis methods
-

Yield: 66%

Reaction Conditions:

Stage #1:6-fluoro-1H-indole;trifluoroacetic anhydride in N,N-dimethyl-formamide at 0; for 3 h;
Stage #2: with sodium hydroxide in N,N-dimethyl-formamide; pH=3 for 4 h;Reflux;

Steps:

1 6-fluoroiindole-3-carboxylic acid (2)
Trifluoroacetic anhydride (9.009 ml, 64.8 mmol, 2.2 equiv.) was added drop wise to a stirring solution of 6-fluoroindole (4.000 g, 29.6 mmol, 1.0 equiv.) in DMF (25 mL) at 0°C (external ice bath temperature). After 3 hours in the ice bath the mixture was quenched with 40 mL of 2N sodium carbonate. The precipitate was collected by filtration and washed with water. The solid was taken up in 4M NaOH (50 mL) and refluxed for 4 hours. The reaction mixture was cooled to room temperature and poured into 50 mL of water. The mixture was cooled in an ice bath and slowly brought to pH 3 with 6N HCl. The precipitate which formed was collected by filtration, washed with water and dried under vacuum to give an off -white solid (3.5 g, 66%). 1H NMR (DMSO-d6, 300 MHz): 12.03 (bs, 1H), 11.87 (s, 1H), 7.99-7.92(m, 2H), 7.23 (dd, J=9.9 & 2.4 Hz, 1Η),7.03-6.97 (m, 1H).

References:

BUCK INSTITUTE FOR RESEARCH ON AGING;JOHN, Varghese;BREDESEN, Dale, E.;SPILMAN, Patricia, R.;JAGODZINSKA, Barbara WO2017/197177, 2017, A1 Location in patent:Paragraph 0219-0221

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