Hydrochloric Acid → (S)-1-(2-Chlorobenzyloxycarbonyl)-piperidine-2-carboxylic acid methyl ester

Temperature

0 °C

To a vigorously stirred solution of (S)-pipecolic acid methyl ester hydrochloride (500 mg, 2.79 mmol) in dry DCM (10 mL) cooled in an ice-bath, was added dropwise Et3N (705 mg, 6.96 mmol) followed by 2-chlorobenzyl chloroformate (made from 2-chlorobenzyl alcohol using the method described in J. Med. Chem., 1998, 41, 1315–1343) (857 mg, 4.18 mmol). The resulting suspension was stirred at 0° C. for a further 0.75 h, diluted with ethyl acetate (30 mL) and poured into 1.0-M HCl (30 mL). The organic layer was separated and washed sequentially with 1.0-M HCl (20 mL), aq.NaHCO3 (20 mL) and brine (20 mL). The organic layer was then dried (NaSO4), filtered and concentrated under reduced pressure to give a colorless oil. The oil was purified by column chromatography (15% ethyl acetate in hexane) to give the title compound as a colorless viscous oil (824 mg, 95%): 1H NMR (400 MHz, CDCl3) 1.2–1.4 (1H, m), 1.4–1.6 (1H, m), 1.6–1.8 (3H, m), 2.2–2.3 (1H, m), 2.9–3.2 (1H, m), 3.7–3.8 (3H, m), 4.0–4.2 (1H, m), 4.8–5.0 (1H, m), 5.2–5.4 (2H, m), 7.2–7.3 (2H, m), 7.3–7.5 (2H, m)

1. customThe organic layer was separated
2. washwashed sequentially with 1.0-M HCl (20 mL)
3. dry with materialThe organic layer was then dried (NaSO4)
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. customto give a colorless oil
7. customThe oil was purified by column chromatography (15% ethyl acetate in hexane)

ORD record

ord-3b41e3d0abb74dbc8029fdc2591a429a

Source dataset

uspto-grants-2006_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07053057B2