tert-Butyl chloroacetate → t-Butyl 3,5-difluoro4-nitrophenylacetate

Temperature

-20 °C

A mixture of potassium tert-butoxide (12.3 g, 111.0 mmol) in NMP (100 ml) was cooled to −20° C. under N2. A mixture of 2,6-difluoronitrobenzene (5.0 g, 31.43 mmol) and tert-butylchloroacetate (7.6 ml, 53.11 mmol) in NMP (100 ml) was added slowly at −10° C. to -20° C. over 1.5 hours. After 1.5 hours the reaction was quenched by pouring into 2M HCl (120 ml) and ice, then heptane (300 ml) was added. The mixture was stirred for 10 minutes, separated and the aqueous extracted with heptane (2×400 ml). The organic layer was washed with brine (×2), dried (MgSO4), filtered and washed with heptane. The solution was concentrated in vacuo and the residue purified by column chromatography (3-4% EtOAc/Heptane) to provide the title compound as an orange oil (4.34 g, 53% yield).

1. additionwas added slowly at −10° C. to -20° C. over 1.5 hours
2. customAfter 1.5 hours the reaction was quenched
3. additionby pouring into 2M HCl (120 ml) and ice
4. additionheptane (300 ml) was added
5. customseparated
6. extractionthe aqueous extracted with heptane (2×400 ml)
7. washThe organic layer was washed with brine (×2)
8. dry with materialdried (MgSO4)
9. filtrationfiltered
10. washwashed with heptane
11. concentrationThe solution was concentrated in vacuo
12. customthe residue purified by column chromatography (3-4% EtOAc/Heptane)

ORD record

ord-d444acf17e2d4a75a6b88ebe4ba39495

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08778953B2