Bromine → 4-Bromo-2,3-difluoroaniline

To a stirred solution of 2,3-difluoroaniline (20 g, 154.9 mmol) in HOAc (230 mL) was added over 1 hour a solution of bromine (24.75 g, 7.978 mL, 154.9 mmol) in HOAc (70 mL) at RT. The reaction mixture was stirred at RT for another 1 hour and a white precipitate appeared. The solvent was removed under reduced pressure, the residue was made basic with 6M NaOH at 0° C., and the basic solution was extracted with DCM. After drying the organics over MgSO4, the volatiles were removed in vacuo to provide 4-bromo-2,3-difluoroaniline (Compound 1079); LC/MS (M+H)=207.96. This compound was reacted with the acyl chloride of 2-fluoronicotinic acid and carried through the sequence of reactions as described in Example 19 to produce N-tert-butyl-3-(1-(4-bromo-2,3-difluorophenyl)-1H-tetrazol-5-yl)pyridin-2-amine (Compound 1080); 1H NMR (300 MHz, DMSO-d6): δ 8.21 (dd, J=1.9, 4.8 Hz, 1H), 7.90-7.84 (m, 1H), 7.54-7.48 (m, 1H), 7.44 (dd, J=1.9, 7.7 Hz, 1H), 6.71 (s, 1H), 6.58 (dd, J=4.8, 7.7 Hz, 1H) and 1.31 (s, 9H).

1. customThe solvent was removed under reduced pressure
2. customwas made basic with 6M NaOH at 0° C.
3. extractionthe basic solution was extracted with DCM
4. dry with materialAfter drying the organics over MgSO4
5. customthe volatiles were removed in vacuo

ORD record

ord-921a216de84f4d339dfe4ca6ecbd1104

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08481524B2