Tetrahydrofuran → 2-(2-Chloro-3-fluoropyridin-4-yl)propan-2-ol

Temperature

-78 °C

A mixture of lithium diisopropylamide (2 M in heptane/THF/ethylbenzene, stabilised with 0.5% w/w LiBr; 1.9 ml, 3.8 mmol) and THF (3 ml) was cooled to −78° C. and a solution of 2-chloro-3-fluoropyridine (500 mg, 3.8 mmol) in THF (3 ml) was added dropwise over 1 min. After 2 h, acetone (pre-dried twice over activated 4 Å molecular sieves) was added dropwise and the mixture allowed to warm to ambient temperature, then quenched with saturated aqueous NH4Cl solution (10 ml) and extracted with EtOAc (50 ml). The organic phase was dried over anhydrous MgSO4 and concentrated in vacuo. The crude material was purified by column chromatography (silica; 10-20% EtOAc/isohexane) to afford 2-(2-chloro-3-fluoropyridin-4-yl)propan-2-ol (687 mg, 95%): δH (360 MHz, CDCl3) 1.66 (6H, s), 7.53 (1H, m), 8.16 (1H, m); m/z (ES+) 190 (100%, [MH]+).

1. dry with materialacetone (pre-dried twice over activated 4 Å molecular sieves)
2. additionwas added dropwise
3. temperatureto warm to ambient temperature
4. customquenched with saturated aqueous NH4Cl solution (10 ml)
5. extractionextracted with EtOAc (50 ml)
6. dry with materialThe organic phase was dried over anhydrous MgSO4
7. concentrationconcentrated in vacuo
8. customThe crude material was purified by column chromatography (silica; 10-20% EtOAc/isohexane)

ORD record

ord-ab7bc9455bb34e63a213a5b5f2ebbeb3

Source dataset

uspto-grants-2007_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07279580B2