Acetone → 2-(5-Chloropyrazin-2-yl)propan-2-ol

Temperature

-78 °C

2-Bromo-5-chloropyrazine (900 mg, 4.65 mmol) was dissolved in toluene (20 mL). The reaction vessel was flushed with nitrogen and cooled to −78° C. n-Butyllithium (2.5M solution in hexanes, 2.23 mL) was added slowly under stirring and allowed to stir for a further 10 minutes upon complete addition. Acetone (3.42 mL, 46.53 mmol) was added and the reaction mixture was stirred at −78° C. for 30 minutes. The reaction mixture was allowed to warm to room temperature and the solvent was removed in vacuo. The residue was taken up in EtOAc (50 mL) and washed using saturated aqueous sodium bicarbonate solution. The organic phase was dried over sodium sulphate, filtered and concentrated in vacuo. The crude brown oil was purified by chromatography on silica (Biotage, 25 g cartridge), eluting with 0 to 100% ethyl acetate in heptanes, to afford the title compound (450 mg, 56%) as a yellow oil. Method B HPLC-MS: MH+ m/z 173, RT 1.31 minutes.

1. customThe reaction vessel was flushed with nitrogen
2. additionwas added slowly
3. stirringto stir for a further 10 minutes upon complete addition
4. stirringthe reaction mixture was stirred at −78° C. for 30 minutes
5. temperatureto warm to room temperature
6. customthe solvent was removed in vacuo
7. washwashed
8. dry with materialThe organic phase was dried over sodium sulphate
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customThe crude brown oil was purified by chromatography on silica (Biotage, 25 g cartridge)
12. washeluting with 0 to 100% ethyl acetate in heptanes

ORD record

ord-e5f1de243ce643959dbdb402f02724fc

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09309243B2