Ammonium Chloride → (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 NH4Cl 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 NH4Cl 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. extractionthe mixture was extracted twice with EtOAc
3. washThe combined organic extracts were washed with brine
4. customdried over anhyd
5. concentrationMgSO4 and concentrated to an oil (5.3 g)
6. additionThe crude oil (2.0 g) was then treated with (Bu)4NF (6 mL, 1M in THF)
7. stirringThe mixture was stirred at rt for 1 h
8. additionsaturated aqueous NH4Cl was added
9. extractionthe mixture was extracted twice with EtOAc
10. washThe combined organic extracts were washed with brine
11. customdried over anhyd
12. concentrationMgSO4 and concentrated to an oil

ORD record

ord-002395ec860749de884e62321fd1c5e0

Source dataset

uspto-grants-2008_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07375134B2