2-Oxobutanoic Acid → Methyl 2-amino-5-methyl-1,3-thiazole-4-carboxylate

Under a nitrogen atmosphere at 0° C., to a solution of 2-oxobutyric acid (12 g, 120 mmol) in methanol was added thionyl chloride (40 mL, 330 mmol), and the mixture was stirred at the same temperature for 3 hr. The solvent was evaporated under reduced pressure. Under a nitrogen atmosphere at 0° C., to a solution (50 mL) of the residue in diethyl ether was slowly added dropwise a solution (50 mL) of bromine (10 g, 130 mmol) in diethyl ether, and the mixture was stirred overnight while allowing the mixture to spontaneously warm. The solvent was evaporated under reduced pressure. An aqueous solution (120 mL) of the residue and thiourea (6.3 g, 83 mmol) was heated under reflux for 3 hr, and cooled to room temperature. The reaction mixture was neutralized with 20% aqueous ammonia solution. The resulting crude title compound was collected by filtration, washed with water to give the title compound (3.3 g, 23%) as a colorless solid.

1. customThe solvent was evaporated under reduced pressure
2. stirringthe mixture was stirred overnight
3. temperatureto spontaneously warm
4. customThe solvent was evaporated under reduced pressure
5. temperatureunder reflux for 3 hr
6. filtrationThe resulting crude title compound was collected by filtration
7. washwashed with water

ORD record

ord-105b28fe59eb47fcab998e5043e04d93

Source dataset

uspto-grants-2013_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08461348B2