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

HRID 602434Notes

Reaction equation

HRID 602434 reaction equation
[Br:1][C:2]1[C:3](=[O:21])[N:4]([C:10]2[CH:11]=[C:12]([CH:17]=[CH:18][C:19]=2[CH3:20])[C:13]([O:15]C)=[O:14])[C:5]([CH3:9])=[CH:6][C:7]=1[OH:8].P([O-])([O-])([O-])=O.[K+].[K+].[K+].[OH-].[Na+].Cl>>[Br:1][C:2]1[C:3](=[O:21])[N:4]([C:10]2[CH:11]=[C:12]([CH:17]=[CH:18][C:19]=2[CH3:20])[C:13]([OH:15])=[O:14])[C:5]([CH3:9])=[CH:6][C:7]=1[OH:8]

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 62657Potassium Phosphate, TribasicHCID 54746388HCID 54746388, compound

Product 1

HCID 54746390(-)3-(3-bromo-4-hydroxy-6-methyl-2-oxopyridin-1(2H)-yl)-4-methylbenzoic acid

Conditions

Temperature
25 °C

Procedure

(+/−)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.

Workup

  1. additionfollowed by the addition of Savinase® enzyme (Novozyme, Bagsvaerd, Denmark)
  2. temperaturewarmed to 30° C
  3. stirringstirred for 30 minutes
  4. customwhich was isolated by filtration
  5. washwashed with water
  6. washThe aqueous filtrate was washed with 5.0 L methylene chloride
  7. customto precipitate

Sources & evidence

ORD record
ord-b276c1e8485d43fd906db28208484922
Source dataset
uspto-grants-2011_03
Patent number
US07906536B2

Reaction notes

Loading…