OXAZOLE-5-CARBOXYLIC ACID synthesis

Yield:118994-90-4 87.5%

Reaction Conditions:

with lithium hydroxide monohydrate;water at 25; for 6.5 h;Large scale;

Steps:

Intermediate 1Oxazole-5-carboxvlic acid
An aqueous solution of lithium hydroxide monohydrate (124.5 kg of a solution preparedfrom 49.44 kg lithium hydroxide monohydrate dissolved in 319 kg water, 398 mol) was added to asolution of ethyl 5-oxazolecarboxylate (54 kg, 382.7 mol) in water (54 kg) maintaining the temperature below 25 °C. The reaction was stirred for 6.5 h and then conc. aqueous HCI (64.8 kg) was added maintaining the temperature below 25 °C, the crystallisation cooled to 5 °C and held forh. The product was filtered off, washed with cold water (88 kg), then isopropanol (171 kg) anddried under vacuum at 50 °C to give the title compound (37.88 kg, 87.S%).1H NMR (400 MHz, DMSO-d6) ppm 13.68 (br. 5., 1 H), 8.59 (5, 1 H), and 7.88 (5, 1 H).

References:

GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED;BREAM, Robert Nicholas;HAYLER, John David;IRONMONGER, Alan Geoffrey;SZETO, Peter;WEBB, Michael Robert;WHEELHOUSE, Katherine Marie Penelope;WILLACY, Robert David WO2016/193255, 2016, A1 Location in patent:Page/Page column 21

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