Acetic Acid → 2(1H)-Quinolinone, 5-[(1R)-2-[(5,6-diethyl-2,3-dihydro-1H-inden-2-yl)amino]-1-hydroxyethyl]-8-hydroxy-, (2Z)-2-butenedioate (1:1)

Participants

Reaction Conditions

Reaction Steps

A 1 L hydrogenation vessel is charged with 40 grams of 8-phenylmethloxy-5-[(R)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-1H-quinolin-2-one benzoate and 400 mL of acetic acid. Palladium on charcoal 5% (5.44 g) is added and the reaction mass is hydrogenated for 2-8 hours until complete conversion to 5-[(R)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-1H-quinolin-2-one. The mixture is filtered over a pad of filter-aid. The filtrate is concentrated at 50-60° C. under vacuum (100 mbar) to a volume of 70-90 mL. This residue is dissolved in 400 mL of ethanol and heated to 50-60° C. A solution of 11.6 g maleic acid in 24 mL ethanol is added and the resulting clear solution is seeded at an internal temperature of 50° C. with a suspension of 350 mg micronised 5-[(R)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-1H-quinolin-2-one in 20 mL isopropanol. The product is crystallized by slow cooling to 0-5° C. Filtration and washing with 50 mL of ethanol followed by 25 mL of isopropanol provides 65 g crude 5-[(R)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-1H-quinolin-2-one maleate which is further purified by crystallization from 1.36 L of ethanol. This gives 24.3 g pure 5-[(R)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-1H-quinolin-2-one maleate as a white crystalline powder.

Provenance & Evidence