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-4b4a3e266f4b4851b31e48a40d84b5d2

Source dataset

uspto-grants-2008_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07351828B2