Hydrochloric Acid → 6-Hydroxy-3-coumaranone

Temperature

5 °C

To a stirred solution of resorcinol (16.0 kg, 145 moles), chloroacetonitrile (13.2 kg, 175 moles) and ethyl acetate (193 kg, 214 L)under nitrogen was added zinc chloride (11.0 kg, 80.8 moles) and the mixture cooled to 5° C. Hydrogen chloride gas (31.2 kg, 855 moles) was bubbled in at such a rate that the internal temperature did not exceed 30° C. The thick slurry was stirred for an additional 2 hours and the solvent removed by vacuum distillation. Water (80 L) was added and the residual ethyl acetate removed by vacuum distillation. The mixture was heated to 60° C. and stirred for 1 hour. The temperature was cooled to 20° C. and then t-butyl methyl ether (146 L, 113 kg) was added and the mixture stirred for 15 minutes. The aqueous layer was separated and the organic layer washed with water (50 L). The layers were separated and the organic layer removed by vacuum distillation. 95% Ethanol (50 L) was added and the distillation continued until all of the t-butyl methyl ether had been removed. Then 95% ethanol (220 L) was added followed by the addition of sodium acetate (21.8 kg, 266 moles) and the mixture heated to reflux for 1 hour. Additional sodium acetate (3.54 kg, 43.2 moles) was added and the mixture refluxed for an additional 1 hour. The mixture was cooled to 5° C. and the solid collected by centrifugation. This was washed with 95% ethanol (51 L), water (800 L), 95% ethanol (29 L) and hexane (30 L). The material was dried at 40° C. under vacuum to afford the desired product (16.5 kg, 75%) which was used without any further purification.

1. customdid not exceed 30° C
2. customthe solvent removed by vacuum distillation
3. additionWater (80 L) was added
4. customthe residual ethyl acetate removed by vacuum distillation
5. temperatureThe mixture was heated to 60° C.
6. stirringstirred for 1 hour
7. temperatureThe temperature was cooled to 20° C.
8. additiont-butyl methyl ether (146 L, 113 kg) was added
9. stirringthe mixture stirred for 15 minutes
10. customThe aqueous layer was separated
11. washthe organic layer washed with water (50 L)
12. customThe layers were separated
13. customthe organic layer removed by vacuum distillation
14. addition95% Ethanol (50 L) was added
15. distillationthe distillation
16. customhad been removed
17. additionThen 95% ethanol (220 L) was added
18. temperaturethe mixture heated
19. temperatureto reflux for 1 hour
20. temperaturethe mixture refluxed for an additional 1 hour
21. temperatureThe mixture was cooled to 5° C.
22. customthe solid collected by centrifugation
23. washThis was washed with 95% ethanol (51 L), water (800 L), 95% ethanol (29 L) and hexane (30 L)
24. customThe material was dried at 40° C. under vacuum

ORD record

ord-9a18f3eb44d646c29ce42cec9b0fd38d

Source dataset

uspto-grants-1997_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05663368