Hydrochloric Acid → (-)3-(3-bromo-4-hydroxy-6-methyl-2-oxopyridin-1(2H)-yl)-4-methylbenzoic acid

Participants

Reaction Conditions

Reaction Steps

(+/−)Methyl 3-(3-bromo-4-hydroxy-6-methyl-2-oxopyridin-1(2H)-yl)-4-methylbenzoate (4) (1 kg, 2.84 moles) was mixed with 1M dibasic potassium phosphate buffer solution (dibasic potassium phosphate (3.05 kg, 17.5 moles) and water (16.4 L)) and warmed to 25° C. The pH of the solution was adjusted to 9.1 with 10% NaOH solution (about 4.2 L) followed by the addition of Savinase® enzyme (Novozyme, Bagsvaerd, Denmark) and warmed to 30° C. After stirring for about 40-45 hours, the pH of the solution was adjusted to 6.0 using 6N HCl (2.3 L) and stirred for 30 minutes. The resulting precipitate was the unreacted enantiomer of the ester methyl (+)3-(3-bromo-4-hydroxy-6-methyl-2-oxopyridin-1(2H)-yl)-4-methylbenzoate (423 gm), which was isolated by filtration and washed with water. The aqueous filtrate was washed with 5.0 L methylene chloride. It was then further acidified to pH 3.6 with 2.1 L of 6N HCl to precipitate and isolate the optically enriched acid (−)3-(3-bromo-4-hydroxy-6-methyl-2-oxopyridin-1(2H)-yl)-4-methylbenzoic acid (10) by filtration. 1.3 kg (80% of theory) of product was obtained after drying.

Provenance & Evidence