6-Chlorooxazolo[4,5-b]pyridin-2(3H)-one

Synthesis

The general procedure for the synthesis of 6-chloro-oxazolo[4,5-b]pyridin-2(3H)-one using 2,3-dihydropyrido[2,3-d][1,3]oxazol-2-one as starting material was as follows: first, DMF (9 L) was added to a 100 L autoclave, a mechanical stirrer was started, and 2,3-dihydropyrido[2,3-d][1,3]oxazol-2-one ( 10 kg) and stirred until completely dissolved. Subsequently, N-chlorosuccinimide (12.16 kg) was dissolved in DMF (30 L) and slowly added dropwise to the reactor, during which the temperature of the reaction was controlled not to exceed 40 °C (cooled by a circulating condensate pump if necessary). After dropwise addition, the reaction mixture was stirred at room temperature overnight. The reaction progress was monitored by TLC and GC. Upon completion of the reaction, water (39 L) was slowly added under cooling conditions and stirring was continued for 60 minutes before filtration. The filter cake was washed twice with water and subsequently dried under vacuum to give a crude product of 11.8 kg.Finally, the crude product was recrystallized by dichloromethane and ethyl acetate to give the pure product 6-chloroxazolo[4,5-b]pyridin-2(3H)-one (11.1 kg) in 89% yield.

References

[1] Patent: CN103709175, 2016, B. Location in patent: Paragraph 0024-0025
[2] Patent: CN103755627, 2016, B. Location in patent: Paragraph 0022; 0023
[3] Patent: WO2018/37223, 2018, A1. Location in patent: Page/Page column 222
[4] Helvetica Chimica Acta, 1976, vol. 59, p. 1593 - 1612