Sodium borohydride → HCID 86671310, compound

6-bromo-3-fluoropicolinaldehyde (4.0 g, 19.61 mmol) and (R)-2-amino-3-methylbutan-1-ol (2.281 mL, 20.59 mmol) were dissolved in methanol (100 mL) and stirred at ambient temperature for 1 hour and 15 minutes. Sodium borohydride (0.742 g, 19.61 mmol) was added and the mixture was stirred for another 1 hour and 30 minutes. The volume of the reaction mixture was reduced, and the mixture was quenched with 200 mL 1.0 N NaOH, and extracted with 200 mL dichloromethane (2×). The organic phase was extracted with 1.0 N HCl and partitioned. The aqueous phase was separated, neutralized with 3.0 N NaOH, extracted with EtOAc, organic phase separated and washed with brine. The organic phase was dried over Na2SO4, filtered, and concentrated to obtain the title compound as an orange solid. MS (ESI+) m/z 291.0 (M+H); 1H NMR (300 MHz, DMSO-d6) δ 7.69 (t, J=8.8, 1H), 7.60 (dd, J=8.6, 3.7, 1H), 4.42 (t, J=5.2, 1H), 3.92-3.75 (m, 2H), 3.43 (dt, J=10.7, 4.8, 1H), 2.34-2.24 (m, 1H), 2.08 (s, 1H), 1.87-1.71 (m, 1H), 0.83 (dd, J=8.5, 6.9, 6H).

1. stirringthe mixture was stirred for another 1 hour and 30 minutes
2. customthe mixture was quenched with 200 mL 1.0 N NaOH
3. extractionextracted with 200 mL dichloromethane (2×)
4. extractionThe organic phase was extracted with 1.0 N HCl
5. custompartitioned
6. customThe aqueous phase was separated
7. extractionextracted with EtOAc, organic phase
8. customseparated
9. washwashed with brine
10. dry with materialThe organic phase was dried over Na2SO4
11. filtrationfiltered
12. concentrationconcentrated

ORD record

ord-b1dcafa51aa940f09838f82798b8ccf3

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09012651B2