3-Bromopyridine → HCID 69656634, compound

Temperature

-78 °C

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).

1. temperaturecooled to −78° C.
2. additionThe contents of Vessel B were added to Vessel A via cannula at −78° C
3. temperatureThe temperature was increased to 0° C.
4. stirringthe mixture stirred for 2.5 hours
5. customThe mixture was then quenched with saturated ammonium chloride solution (40 mL)
6. extractionextracted with EtOAc
7. customThe EtOAc was evaporated in vacuo
8. customthe residue dried
9. custompurified on silica gel using a 1:1
10. addition2:1 mixture of EtOAc to hexane as mobile phase
11. customPooled fractions were dried to yield

ORD record

ord-1636b95dadd2433c90cfb5b927dad151

Source dataset

uspto-grants-2006_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07144899B2