Pyridine → 4-Nitrophenyl 1,3-thiazol-5-ylmethyl carbonate

Participants

Reaction Conditions

Reaction Steps

A solution comprising 21.0 Kg. (104 mole) 4-nitrophenyl chloroformate dissolved into 75 L ethyl acetate was prepared. The solution was cooled to -5° C. and 0.4 Kg (4 mole) of pyridine dissolved, into 18 L ethyl acetate, was added. The resulting slurry was stirred at -5°±5° C. After 1 hour, 5-hydroxymethyl thiazole 10.0 Kg (87 mole), (HMT) dissolved into 75 L ethyl acetate, was added over 30-40 minutes, maintaining the reaction mixture temperature at -5°±3° C. The resulting slurry was then warmed to 0°±5° C., and stirred for at least about 24 hours. The reaction was checked for completion by HPLC. Upon completion, absolute ethanol, 32 Kg, was added to the slurry (about 15-20% of the total reaction volume), stirred for at least about 2 hours, and then centrifuged or filtered. The product solid was washed with cold ethyl acetate (2×75 L) and dried at 40°±5° C. to an LOD <2%. Yield: 25.15 Kg (93%).

Provenance & Evidence