Hydrochloric Acid → 2-(5-Bromopyridin-3-yl)-1,1,1-trifluoropropan-2-ol

To a solution of 1-(5-bromo-pyridin-3-yl)-ethanone (1.0 g, 5.0 mmol) in THF (dry, 25 ml) at room temperature is added tetrabutyl-ammonium fluoride (0.35 ml, 1M in THF, 0.35 mmol). Then trimethyl-trifluoromethyl-silane (3.25 ml, 2.0M in THF, 6.5 mmol) is added to the reaction mixture dropwise. The reaction mixture is stirred for 3 h. Then HCl (4N, 6.6 ml, 26.5 mmol) is added to the mixture. The reaction mixture is stirred for 4 h at room temperature and then is neutralized by adding Na2CO3 powder slowly. The resulting mixture is partitioned between water and EtOAc, and the aqueous phase is extracted with EtOAc. The combined organic phases are concentrated in vacuo. The crude mixture is separated by flash silica gel column (EtOAc/Heptane 0 to 30% gradient, then 30%) to obtain 1.12 g 2-(5-bromo-3-pyridyl)-1,1,1-trifluoro-propan-2-ol.

1. stirringThe reaction mixture is stirred for 4 h at room temperature
2. customThe resulting mixture is partitioned between water and EtOAc
3. extractionthe aqueous phase is extracted with EtOAc
4. concentrationThe combined organic phases are concentrated in vacuo
5. customThe crude mixture is separated by flash silica gel column (EtOAc/Heptane 0 to 30% gradient

ORD record

ord-1769880856144cde8552b969d287308d

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09181272B2