Acetaminophen → HCID 10013467, compound

Temperature

0 °C

A solution of 4-acetominophenol (75.0 g), phosgene solution (450 mL, 20% in toluene), and ethyl acetate (1875 mL) was cooled to 0° C. N,N-Diethylaniline (94.7 mL) was added dropwise and the reaction was stirred at 0° C. for two hours. The reaction was then allowed to warm to room temperature. An aliquot for NMR analysis was taken four hours post addition. The reaction remained incomplete and was stirred at room temperature overnight. An-aliquot for NMR analysis after overnight stirring indicated no change had occurred in the reaction since the previous aliquot. The reaction was heated to 40° C. until phosgene gas evolution ceased (approximately 30 minutes). The reaction was cooled to room temperature and was then filtered. The filter cake was washed with ethyl acetate. NMR analysis of the filtered solid indicated it was N,N-diethylaniline related material. The filtrate was washed was washed with 0.1N HCl (375 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo to afford a pale yellow solid. The solid was triturated using ether (375 mL) for twenty minutes at room temperature. The solid was filtered and washed with ether. NMR analysis indicated product with residual ether remaining. The solid was dried overnight in a vacuum oven at ambient temperature to afford 77.55 g (73.3% yield). NMR and MS analysis indicated product. 1H NMR (300 MHz, CDCl3+DMSO-d6): δ9.18 (s, 1H), 7.62 (d, 2H), 7.15 (d, 2H), 2.18 (s, 3H); MS m/z: 214 (M+H)+.

1. temperatureto warm to room temperature
2. additionAn aliquot for NMR analysis was taken four hours post addition
3. stirringwas stirred at room temperature overnight
4. stirringAn-aliquot for NMR analysis after overnight stirring
5. customhad occurred in the reaction since the previous aliquot
6. custom(approximately 30 minutes)
7. temperatureThe reaction was cooled to room temperature
8. filtrationwas then filtered
9. washThe filter cake was washed with ethyl acetate
10. washThe filtrate was washed
11. washwas washed with 0.1N HCl (375 mL)
12. dry with materialThe organic layer was dried over sodium sulfate
13. filtrationfiltered
14. concentrationconcentrated in vacuo
15. customto afford a pale yellow solid
16. customThe solid was triturated
17. customfor twenty minutes
18. customat room temperature
19. filtrationThe solid was filtered
20. washwashed with ether
21. customThe solid was dried overnight in a vacuum oven at ambient temperature
22. customto afford 77.55 g (73.3% yield)

ORD record

ord-1931ea57c1cb4f45838c0fea43cb7f8a

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08993545B2