Phenylmethyl 2-(4-fluorophenyl)-3,4-dihydro-4-oxo-1(2H)-pyridinecarboxylate → HCID 82657288, compound

A mixture of benzyl 2-(4-fluorophenyl)-4-oxo-3,4-dihydropyridine-1(2H)-carboxylate (1.00 g, 3.07 mmol) (reagent preparation 20) and 5% Pd on carbon (0.1 g) in acetic acid:methanol 1:10 (20 mL) was hydrogenated at 45 psi using a Parr apparatus for 16 hours. The catalyst was removed by filtering through Celite, and the filtrate concentrated to give (±)-(2S,4R)-2-(4-fluorophenyl)piperidin-4-ol as an oil. The material was taken into chloroform (100 mL) and di-tert-butyl dicarbonate (0.74 g, 3.4 mmol) was added, followed by the dropwise addition of diisopropylethylamine (1.5 g, 12 mmol). The reaction was warmed to reflux for 10 minutes, then allowed to cool to 25° C. over 30 minutes. The organic solution was washed with 0.1M aqueous hydrochloric acid (45 mL), water (50 mL) and saturated sodium bicarbonate (50 mL), then dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography (ethyl acetate:hexanes, 1:1) to give (±)-(2S,4R)-tert-butyl 2-(4-fluorophenyl)-4-hydroxypiperidine-1-carboxylate (0.59 g, 65% yield). 1H NMR (400 MHz, d6-DMSO): 7.25 (m, 2H), 7.10 (m, 2H), 4.96 (t, 1H), 4.46 (d, 1H), 3.90 (m, 1H), 3.77 (m, 1H), 3.23 (dt, 1H), 2.06 (m, 1H), 1.95 (m, 1H) 1.73 (m, 1H), 1.45 (m, 1H), 1.29 (s, 9H).

1. customfor 16 hours
2. customThe catalyst was removed
3. filtrationby filtering through Celite
4. concentrationthe filtrate concentrated

ORD record

ord-a08c7298b4694b8c901e655512e90c83

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08637499B2