Acetaldehyde → 1-(3-Bromo-5-Fluoro-pyridin-4-yl)-ethanol

Temperature

-40 °C

n-BuLi (1.6M in hexanes) (19.60 ml, 31.4 mmol) was added dropwise to a solution of diisopropylamine (4.84 ml, 34.0 mmol) in THF (87 ml) at −78° C. under N2. The resulting mixture was warmed up to −40° C. and stirred for 10 min and recoiled to −78° C. 3-bromo-5-fluoropyridine (4.6 g, 26.1 mmol) in 5 mL THF was added dropwise at this temperature. After 30 min, acetaldehyde (2.95 ml, 52.3 mmol) was added dropwise and the resulting mixture was stirred for 30 min at −78° C., and then for another 30 min at 0° C. The mixture was quenched with saturated NH4Cl solution and extracted with EtOAc two times, dried over magnesium sulfate, filtered, concentrated. The residue was purified via Biotage (SNAP50, 0-30% AcOEt/heptane, v/v) giving the title compound 4a (2.869 g, 50%) as yellow oil. LC-MS (M+1) 221.9, t=1.01 min.

1. customrecoiled to −78° C
2. waitAfter 30 min
3. stirringthe resulting mixture was stirred for 30 min at −78° C.
4. waitfor another 30 min at 0° C
5. customThe mixture was quenched with saturated NH4Cl solution
6. extractionextracted with EtOAc two times
7. dry with materialdried over magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated
10. customThe residue was purified via Biotage (SNAP50, 0-30% AcOEt/heptane, v/v)

ORD record

ord-5a20890e608b44d6ba47d0910cc0e401

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08519134B2