Water → Tert-butyl 4-bromo-2,6-difluorobenzoate

Temperature

-78 °C

To a solution of diisopropylamine (17.9 mL, 0.12 mol) in anhydrous THF at −78° C. was added n-BuLi (45.5 mL, 0.11 mol, 2.5 M in hexane) dropwise, over period of 15 min and the resulting solution was stirred at −78° C. for 30 mins. To this was added 1-bromo-3,5-difluoro benzene (20.0 g, 0.10 mol) in THF (30 mL) dropwise and it was stirred for 1 h. Finally, Boc-anhydride (26.0 mL, 0.11 mol) was added to it and the reaction mixture was slowly allowed to come to room temperature over a period of 2 h. After completion of the reaction, it was diluted with water (100 mL) and extraction was carried out using diethyl ether (300×2). The combine organic layers were washed with water (250 mL), brine (250 mL) and dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to provide crude VII-5-IV (26 g) as a brown liquid, which was used for next step with out any purification. 1H NMR (DMSO-d6, 400 MHz) δ 1.42 (s, 9H), 7.63 (d, J=8.0 Hz, 2H).

1. stirringit was stirred for 1 h
2. waitto come to room temperature over a period of 2 h
3. customAfter completion of the reaction, it
4. washThe combine organic layers were washed with water (250 mL), brine (250 mL)
5. dry with materialdried over anhydrous Na2SO4
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customto provide crude VII-5-IV (26 g) as a brown liquid, which
9. customwas used for next step with out any purification

ORD record

ord-f3ad91d7a9244705814651f65e24d85f

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09233983B2