3-Bromopyridine → HCID 69656634, compound

Participants

Reaction Conditions

Reaction Steps

tert-Butyl 1-[(3-chlorophenyl)(oxo)acetyl]-L-prolinate (2.2 g, 6.46 mmol) was dissolved in THF (10 mL) and cooled to −78° C. under a nitrogen atmosphere (Vessel A). In a separate vessel containing 3-bromopyridine (0.68 mL, 7.1 mmol) in ethyl ether (50 mL) cooled to −78° C. was added n-BuLi (2.5M in hexanes, 3.1 mL, 7.7 mmol) and the mixture was stirred for one hour (Vessel B). The contents of Vessel B were added to Vessel A via cannula at −78° C. The temperature was increased to 0° C. and the mixture stirred for 2.5 hours. The mixture was then quenched with saturated ammonium chloride solution (40 mL) and extracted with EtOAc. The EtOAc was evaporated in vacuo, and the residue dried and purified on silica gel using a 1:1 then 2:1 mixture of EtOAc to hexane as mobile phase. Pooled fractions were dried to yield: Nonpolar isomer of tert-butyl 1-[(3-chlorophenyl)(hydroxy)pyridin-3-ylacetyl]-L-prolinate (0.43 g, HPLC RT=3.01 min, Method A; LCMS m/z=417). Polar isomer of ten-butyl 1-[(3-chlorophenyl)(hydroxy)pyridin-3-ylacetyl]-L-prolinate (0.12 g, HPLC RT=2.96 min, Method A; LCMS m/z=417).

Provenance & Evidence