Potassium Carbonate → HCID 19065954, compound

Participants

Reaction Steps

A solution of N,N-dimethyl-2-chloroacetamide (28 g) in acetone (300 mL) was added dropwise during 1 hour to a mixture of 5-chloro-1-(4-fluorophenyl)-3-hydroxy-1H-indole-2-carboxylic acid methyl ester (64 g) (prepared according to the method of Unangst et al. J.Heterocyc.Chem. 1984, 21, 709-714 and 1987, 24, 811-815) and potassium carbonate (40 g) in acetone (500 mL) kept at reflux. The mixture was refluxed for another 3 hours and subsequently worked-up. The resulting crude acetamide derivative crystallized from cyclohexane. Yield 72 g. Mp: 124°-125° C. To a suspension of LiAlH4 pellets (10 g) in dry THF (200 mL) kept at gentle reflux was added dropwise a solution of the acetamide derivative (35 g) in dry THF (300 mL). After reflux for 2 hours the mixture was cooled on an ice bath and excess LiAlH4 was hydrolyzed by cautiously adding a mixture of 10% water in THF. Inorganic salts were filtered off and the solvent evaporated in vacuo leaving the title compound as a visceous oil. Yield: 19 g. The hydrochloric acid salt of the title compound 9 crystallized from acetone by addition of a solution of hydrogenchloride gas in diethyl ether.mp 185°-186° C.; 1H NMR (DMSO-d6) δ 2.90 (s, 6H), 3.60 (t, 2H), 4.40 (s, 2H), 4.45 (t, 2H), 7.05 (d, 1H), 7.10 (dd, 1H), 7.40 (t, 2H), 7.55 (dd, 2H), 7.85 (d, 1H). MS (m/z) 363 (MH+), 72 (100); Anal (C19H20ClFN2O2.HCl) C, H, N.

Provenance & Evidence