Sodium borohydride → 6-Bromo-1,2,3,4-tetrahydro-1,8-naphthyridine

To a cooled (0° C.) solution of 6-bromo-3,4-dihydro-1H-[1,8]naphthyridin-2-one (10.0 g, 44.0 mmol) in THF (500 mL) is added sodium borohydride (8.3 g, 220 mmol) followed by boron trifluoride diethyl ether complex (38.7 mL, 308 mmol), dropwise. The resulting mixture is allowed to warm and stir at room temperature for 16 h. The reaction is carefully quenched with the dropwise addition of 1N HCl (15 mL). Once quenched, additional 1N HCl (85 mL) is added and the mixture is stirred at room temperature for 16 h. The mixture is concentrated, diluted with water and made basic (pH 8) with the addition of powdered sodium bicarbonate. The mixture is extracted with EtOAc and the combined organic layers are washed with brine, dried (Na2SO4) and concentrated to obtain the title compound (9.3 g).

1. temperatureto warm
2. customThe reaction is carefully quenched with the dropwise addition of 1N HCl (15 mL)
3. customOnce quenched
4. additionadditional 1N HCl (85 mL) is added
5. stirringthe mixture is stirred at room temperature for 16 h
6. concentrationThe mixture is concentrated
7. additiondiluted with water
8. additionwith the addition of powdered sodium bicarbonate
9. extractionThe mixture is extracted with EtOAc
10. washthe combined organic layers are washed with brine
11. dry with materialdried (Na2SO4)
12. concentrationconcentrated

ORD record

ord-76a4ec175174490391f8a7769f24dac3

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09181272B2