tert-Butyl 4-oxopiperidine-1-carboxylate → tert-Butyl4-hydroxy-4-[4-(trifluoromethyl)pyridin-2-yl]piperidine-1-carboxylate

Temperature

-78 °C

To a slightly cloudy solution of 2-bromo-4-(trifluoromethyl)pyridine (4.0 g, 14.2 mmol) in dry methylene chloride (52.7 mL) cooled at −78° C. was added a 1.6 M solution of n-butyllithium in hexanes (9.65 mL). After being stirred for 40 min at −78° C., a solution of tert-butyl 4-oxo-1-piperidinecarboxylate (2.59 g, 12.9 mmol) in dry methylene chloride (10.0 mL) was added dropwise. The reaction was stirred at −78° C. for 1 h and quenched with aqueous NH4Cl. THF was removed by rotary evaporation. The aqueous layer was extracted with methylene chloride three times. The combined organic layers were dried, filtered and concentrated. The residue was purified by column chromatography on silica gel (30:70 EtOAc/hexanes) to give 2.63 g (59%) of desired product as a brown oil. LC-MS calculated for C16H21F3N2O3: (M+H) 347; found 247.0 (M-Boc+1).

1. stirringThe reaction was stirred at −78° C. for 1 h
2. customquenched with aqueous NH4Cl
3. customTHF was removed by rotary evaporation
4. extractionThe aqueous layer was extracted with methylene chloride three times
5. customThe combined organic layers were dried
6. filtrationfiltered
7. concentrationconcentrated
8. customThe residue was purified by column chromatography on silica gel (30:70 EtOAc/hexanes)

ORD record

ord-88daf1e6817a4c4aaeb66db46ad42ecf

Source dataset

uspto-grants-2008_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07449467B2