Lithium hydroxide, monohydrate → 1-[4'-(2"-Ethyl-5",7"-dimethylimidazo[4,5-b]pyridin-3-yl)methylphenyl]cyclopent-3-ene-1-carboxylic acid

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Reaction Steps

A solution of the product of Step 3A, above (52 g, 134 mmol), and lithium hydroxide monohydrate (56.5 g) in 1350 ml of methanol and 1350 ml of water was heated to reflux for 3.5 hours. The reaction mixture was concentrated in vacuo to about one third of its original volume and the residue was washed with ether. The aqueous layer was adjusted to pH 4 with concentrated hydrochloric acid and acetic acid and was extracted three times with ethyl acetate-THF. The combined organic layers were washed with saturated sodium chloride solution and were dried over magnesium sulfate. Concentration afforded the title compound as a pale yellow solid which was purified as follows. The crude title compound (83 g) was suspended in 650 ml of ortho-dichlorobenzene and heated to reflux for 14 hours, then was allowed to cool slowly to room temperature over 6 hours. The precipitate that formed was filtered off and was washed with ethyl acetate. Two recrystallizations from ethyl acetate-THF afforded the purified title compound (45 g) as a colorless solid, mp 233°-234° C.

Provenance & Evidence