Water → Tert-butyl 2-(2-chloro-4-nitrophenoxy)ethyl(2,4-difluorobenzyl)carbamate

Temperature

-2.5 °C

Sodium hydride (0.101 g, 3.83 mmol, 95% in oil) was added to N,N-dimethyl formamide (20 mL) at −5 to 0° C. under nitrogen. The suspension was stirred for 10 minutes and to the resulting cooled mixture was added a solution of tert-butyl 2,4-difluorobenzyl(2-hydroxyethyl)carbamate (1.1 g, 4.21 mmol) in N,N-dimethylformamide (10 mL), maintaining the temperature at −5 to 0° C. during addition. The reaction mixture was stirred further for 20 minutes and then a solution of 3-chloro-4-fluoro-nitrobenzene (0.67 g, 3.83 mmol) in N,N-dimethyl formamide (10 mL), was added dropwise, maintaining the temperature in the range −5 to 0° C. The reaction mixture was allowed to warm to room temperature and stirred for 30 minutes. Water (300 mL) was then added to the reaction mixture and the resulting mixture was extracted with EtOAc (3×50 mL). The combined organic extracts were washed with brine (2×30 mL), dried (Na2SO4) and evaporated under reduced pressure. The residue was purified by column chromatography on neutral silica gel using 5-20% EtOAc in hexane to give the title compound (1.8 g, 60%).

1. temperaturecooled mixture
2. additionduring addition
3. stirringThe reaction mixture was stirred further for 20 minutes
4. temperaturemaintaining the temperature in the range −5 to 0° C
5. temperatureto warm to room temperature
6. stirringstirred for 30 minutes
7. extractionthe resulting mixture was extracted with EtOAc (3×50 mL)
8. washThe combined organic extracts were washed with brine (2×30 mL)
9. dry with materialdried (Na2SO4)
10. customevaporated under reduced pressure
11. customThe residue was purified by column chromatography on neutral silica gel using 5-20% EtOAc in hexane

ORD record

ord-031bb321d0d24b209bd49008cfe1339c

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08716287B2