N-Bromosuccinamide → 5-Bromo-3-(difluoromethoxy)pyridin-2-amine

Temperature

0 °C

N-Bromosuccinamide (1.00 g, 5.62 mmol) was added portionwise over 10 min to a cooled solution of 3-(difluoromethoxy)pyridin-2-amine (1.12 g) in dry acetonitrile (20 ml) at 0° C. The reaction mixture was further stirred at 0° C. for 10 min. The mixture was concentrated, and residue was partitioned between EtOAc/sat. Na2CO3/H2O (30 ml/15 ml/15 ml). The organic phase was sequentially washed with sat. aqueous Na2CO3/H2O (15 ml/15 ml) and brine (30 ml), dried (Na2SO4), and concentrated. The resulting residue was extracted with EtOAc/hexanes (6 ml/30 ml), and the resulting suspension was filtered through Celite, and the resulting filtrate was concentrated to provide 1.32 g (80%) of 5-bromo-3-(difluoromethoxy)pyridine-2-amine. LCMS (m/z, MH+): 238.9, tR=0.52 min; 1H NMR (CDCl3, 400 MHz) δ 7.99 (d, J=2.0 Hz, 1H), 7.41 (m, 1H), 6.50 (t, J=72.8 Hz, 1H), 4.75 (br s, 2H).

1. concentrationThe mixture was concentrated
2. customresidue was partitioned between EtOAc/
3. washThe organic phase was sequentially washed with sat. aqueous Na2CO3/H2O (15 ml/15 ml) and brine (30 ml)
4. dry with materialdried (Na2SO4)
5. concentrationconcentrated
6. extractionThe resulting residue was extracted with EtOAc/hexanes (6 ml/30 ml)
7. filtrationthe resulting suspension was filtered through Celite
8. concentrationthe resulting filtrate was concentrated

ORD record

ord-d86f1c617fa94ad2bed51c40b0400ac6

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08865732B2