2-Bromopyridine → alpha-(4-Fluorophenyl)-alpha-(2-pyridyl)-4-piperidinemethanol

Temperature

-65 °C

To a stirred solution of 36.3 g (0.23 mole) of 2-bromopyridine in 500 ml of anhydrous tetrahydrofuran (THF) at -65° C. was added 88 ml (0.22 mole) of a commercial solution of 2.5M n-butyllithium in hexane at such a rate that the temperature did not exceed -60° C. The dark solution was stirred at -65° C. for 1 h and then treated dropwise with a solution of 24.9 g (0.1 mole) of 1-acetyl-4-(4-fluorobenzoyl)piperidine in 250 ml of THF at such a rate that the temperature did not exceed -60° C. The mixture was stirred for 1 h at -65° C. and overnight at ambient temperature. The dark mixture was poured into 2 L of a saturated ammonium chloride solution. The layers were separated and the aqueous layer was extracted once with a 500-ml portion of methylene chloride. The combined organic layers were washed successively with 500 ml of water, 500 ml of a 4% sodium hydroxide solution, 250 ml of water, and 250 ml brine.

1. customdid not exceed -60° C
2. customdid not exceed -60° C
3. stirringThe mixture was stirred for 1 h at -65° C. and overnight at ambient temperature
4. customThe layers were separated
5. extractionthe aqueous layer was extracted once with a 500-ml portion of methylene chloride
6. washThe combined organic layers were washed successively with 500 ml of water, 500 ml of a 4% sodium hydroxide solution, 250 ml of water, and 250 ml brine

ORD record

ord-da06016d2c214c808acf758b3460b112

Source dataset

uspto-grants-1991_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05057524