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

HRID 965400Notes

Reaction equation

Cl[C:2]([O:4][C:5]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][CH:6]=1)=[O:3].C(OCC)(=O)C.N1C=CC=CC=1.[OH:26][CH2:27][C:28]1[S:32][CH:31]=[N:30][CH:29]=1>C(O)C>[CH:7]1[C:8]([N+:11]([O-:13])=[O:12])=[CH:9][CH:10]=[C:5]([O:4][C:2]([O:26][CH2:27][C:28]2[S:32][CH:31]=[N:30][CH:29]=2)=[O:3])[CH:6]=1

Participants

Conditions

Temperature: -5 °C

Procedure

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%).

Workup

customwas prepared
additionwas added
additionwas added over 30-40 minutes
temperaturemaintaining the reaction mixture temperature at -5°±3° C
temperatureThe resulting slurry was then warmed to 0°±5° C.
stirringstirred for at least about 24 hours
stirringstirred for at least about 2 hours
filtrationfiltered
washThe product solid was washed with cold ethyl acetate (2×75 L)
customdried at 40°±5° C. to an LOD <2%

Sources & evidence

ORD record: ord-95d9bdc56332409caa82182f240ce5df
Source dataset: uspto-grants-1998_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05773625

Reaction notes

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