5-Bromo-2-chloropyridine → (2S)-2-{[(1S)-1-(6-chloropyridin-3-yl)-2,2,2-trifluoroethyl]amino}-4-methylpentan-1-ol

Temperature

-78 °C

To a solution of 5-bromo-2-chloropyridine (2.5 g, 13 mmol) in ether (30 mL) at −78° C. was added n-butyllithium (13 mmol, 2.5 M in hexane). The mixture was stirred at −78° C. for 1 h. (2S)-1-{[tert-butyl(dimethyl)silyl]oxy}-4-methyl-N-[(1E)-2,2,2-trifluoroethylidene]pentan-2-amine (3.64 g, 11.7 mmol, see Step 2, Example 8) was added. The mixture was stirred at −78° C. for 2 h. Saturated aqueous NH4C1 was added to the reaction mixture and the mixture was extracted twice with EtOAc. The combined organic extracts were washed with brine, dried over anhyd. MgSO4 and concentrated to an oil (5.3 g). The crude oil (2.0 g) was then treated with (Bu)4NF (6 mL, 1M in THF). The mixture was stirred at rt for 1 h, saturated aqueous NH4C1 was added and the mixture was extracted twice with EtOAc. The combined organic extracts were washed with brine, dried over anhyd. MgSO4 and concentrated to an oil. Chromatography (20% EtOAc/hexane) afforded the title compound.

1. additionwas added
2. additionSaturated aqueous NH4C1 was added to the reaction mixture
3. extractionthe mixture was extracted twice with EtOAc
4. washThe combined organic extracts were washed with brine
5. customdried over anhyd
6. concentrationMgSO4 and concentrated to an oil (5.3 g)
7. additionThe crude oil (2.0 g) was then treated with (Bu)4NF (6 mL, 1M in THF)
8. stirringThe mixture was stirred at rt for 1 h
9. additionsaturated aqueous NH4C1 was added
10. extractionthe mixture was extracted twice with EtOAc
11. washThe combined organic extracts were washed with brine
12. customdried over anhyd
13. concentrationMgSO4 and concentrated to an oil

ORD record

ord-581b1cc1aea74d179b51884cfaea4e46

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08772336B2