Carbon Dioxide → N-Methoxy-N,1-dimethyl-1H-1,2,3-triazole-5-carboxamide

Temperature

-45 °C

A solution of 1-methyl-1H-1,2,3-triazole (12.9 g, 155 mmol) in THF (260 mL) was cooled to −45° C. Maintaining a temperature of <−35° C., n-BuLi (62.1 mL, 2.5 M in hexanes, 155 mmol) was added over 10 minutes. The reaction mixture was stirred for 30 minutes with cooling to −45° C. and then treated with a sub-surface stream of CO2(g) for a period of 2 hours. After flushing the −35° C. slurry with N2(g) for 5 minutes, thionyl chloride (11.8 mL, 163 mmol) was added. The mixture was allowed to warm to room temperature with stirring over 1.25 hours. Then, N,O-dimethylhydroxylamine hydrochloride (18.14 g, 186 mmol) and N,N-diisopropylethylamine (68.3 mL, 396 mmol) were added and the resulting mixture stirred for 15 hours. Aqueous sodium carbonate (500 mL, 10 wt %) was then added, and the layers were mixed and separated. The aqueous layer was washed with dichloromethane (250 mL and then 125 mL), and the combined organic layers were dried over MgSO4, filtered, and concentrated. The residue was taken up in ethyl acetate (225 mL), treated with MgSO4, and filtered through a pad of silica gel (115 g). The silica gel pad was washed with additional ethyl acetate (800 mL). The eluent was concentrated to provide the title compound as a yellow solid.

1. additionwas added over 10 minutes
2. customAfter flushing the −35° C. slurry with N2(g) for 5 minutes
3. temperatureto warm to room temperature
4. stirringwith stirring over 1.25 hours
5. stirringthe resulting mixture stirred for 15 hours
6. additionthe layers were mixed
7. customseparated
8. washThe aqueous layer was washed with dichloromethane (250 mL
9. dry with material125 mL), and the combined organic layers were dried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated
12. additiontreated with MgSO4
13. filtrationfiltered through a pad of silica gel (115 g)
14. washThe silica gel pad was washed with additional ethyl acetate (800 mL)
15. concentrationThe eluent was concentrated

ORD record

ord-31ea3091d98547f68ce4f082cf3d2ca4

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09284308B2