Ethyl chloroformate → Ethyl-[2-chloro-3-nitro-6-(trifluoromethyl)-pyridin-4-yl]-benzylcarbamate

Temperature

-5 °C

Benzyl-(2-chloro-3-nitro-6-trifluoromethyl-pyridin-4-yl)-amine (57 gm 170 mmol) was dissolved in tetrahydrofuran (750 mL) and stirred under N2. Cooled in an ice/salt bath to −5° C. To this solution was added drop wise over a period of ˜30 minutes, a solution of potassium t-butoxide (21.2 gm, 189 mmol) in tetrahydrofuran (200 mL), maintaining the temperature between −5° and 0° C. to give a deep red reaction mixture. Stirred at this temperature for 15 minutes before the drop wise addition of a solution of ethyl chloroformate (21.4 gm, 198 mmol) in tetrahydrofuran (100 mL), keeping the temperature below 5° C. The cooling bath was removed and the reaction mixture was allowed to reach ambient temperature over 1 hour to give a light brown hazy solution. Evaporation of the solvent was followed by partition of the residue between saturated brine (50 mL) and t-butyl methyl ether (300 mL). The organic phase was washed with water (50 mL) followed by saturated brine (50 mL), dried over sodium sulphate, filtered and evaporated to give a brown oil. The oil was dissolved in n-pentane (250 mL) and stored at ambient temperature overnight. The n-pentane solution was decanted from a dark brown tar which had precipitated out. Evaporation of the solvent gave ethyl-[2-chloro-3-nitro-6-(trifluoromethyl)-pyridin-4-yl]-benzylcarbamate as a pale brown viscous oil (63 gm, 91% yield).

1. additionTo this solution was added drop wise over a period of ˜30 minutes
2. customto give
3. customa deep red reaction mixture
4. customthe temperature below 5° C
5. customThe cooling bath was removed
6. customto give a light brown hazy solution
7. customEvaporation of the solvent
8. customby partition of the residue between saturated brine (50 mL) and t-butyl methyl ether (300 mL)
9. washThe organic phase was washed with water (50 mL)
10. dry with materialdried over sodium sulphate
11. filtrationfiltered
12. customevaporated
13. customto give a brown oil
14. waitstored at ambient temperature overnight
15. customThe n-pentane solution was decanted from a dark brown tar which
16. customhad precipitated out
17. customEvaporation of the solvent

ORD record

ord-99c0c63a5b4b4e04a3f93a07d9a1467a

Source dataset

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08372836B2