2-Bromopyridine → Benzyl 4-hydroxy-4-(pyridin-2-yl)piperidine-1-carboxylate

Temperature

-60 °C

A solution of 2-bromopyridine (0.47 mL, 5 mmol) in THF (20 mL) was cooled to −60° C. and treated dropwise with nBuLi (1.6M in hexanes, 5.2 ml, 5.2 mmol). The reaction mixture was stirred for 30 minutes at −60° C. and then benzyl 4-oxo-1-piperidine carboxylate 1.14 g, 4.9 mmol) in THF (10 mL) was slowly added to the reaction mixture. The reaction mixture was stirred at −60° C. for 15 minutes and then quenched with saturated NH4Cl. The cooling bath was removed and reaction mixture was allowed to warm to room temperature. The mixture was were extracted with CH2Cl2 and the organics were dried (MgSO4), filtered and the filtrate concentrated under reduced pressure. The residue was purified by flash chromatography using hexane:ethyl acetate (1:1) to provide the title compound, 400 mg (27%). 1H NMR (d6-DMSO, 300 MHz) δ 1.54 (m, 4H), 2.05 (m, 4 H), 3.25 (m, 4H), 3.95 (m, 4H), 5.11 (s, 2H), 5.35 (s, 1H), 7.25 (m, 2H), 7.35 (m, 5H), 7.68 (m, 1H), 7.79 (m, 1H), 8.5 (m, 1H); MS (DCI/NH3) m/z 313 (M+H)+.

1. stirringThe reaction mixture was stirred at −60° C. for 15 minutes
2. customquenched with saturated NH4Cl
3. customThe cooling bath was removed
4. customreaction mixture
5. temperatureto warm to room temperature
6. extractionThe mixture was were extracted with CH2Cl2
7. dry with materialthe organics were dried (MgSO4)
8. filtrationfiltered
9. concentrationthe filtrate concentrated under reduced pressure
10. customThe residue was purified by flash chromatography

ORD record

ord-5bc20d793d3242499ef458ded2196c43

Source dataset

uspto-grants-2006_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07022728B2