Hexane → t-Butyl 3-(4-fluorobenzylidene)-1-piperidinecarboxylate

Temperature

0 °C

To a stirred solution of (4-fluorophenylmethyl)triphenylphosphonium chloride (17.68 g, 43.5 mmol) in dry tetrahydrofuran (60 mL) at −78° C. was added 2.5 M n-butyllithium in hexane (14.6 mL, 36.5 mmol). The reaction was warmed to 0° C. for 1 hr. After tis time, t-butyl 3-oxo-1-piperidinecarboxylate (3.46 g, 17.4 mmol) in tetrahydrofuran (60 mL) was added. The mixture was stirred at room temperature for 1 hr and then heated to reflux for 16 hr. The reaction was cooled to room temperature and quenched by the addition of saturated aqueous ammonium chloride. The reaction was extracted with ethyl acetate three times (100 mL). The organic layers were combined, washed with brine, dried over magnesium sulfate, and evaporated in vacuo to a pale yellow oil. The oil was purified by flash chromatography (silica gel, hexane:ethyl acetate 9:1) to yield 3.82 g of a mixture of E and Z isomers as a colorless oil. 1H NMR (300 MHz, CDCl3) δ 7.22-7.14 (m, 2H), 7.04-6.98 (m, 2H), 6.36 (s, 0.33H), 6.28 (s, 0.67H), 4.14 (s, 1.34H), 4.00 (s, 0.66H) 3.50 (t, J=5, 2H), 2.47 (t, J=5, 0.66H), 2.39 (t, J=5, 1.34H), 1.75-1.68 (m, 1.34H), 1.65-1.57 (m, 0.66H), 1.48 (s, 9H).

1. temperatureheated
2. temperatureto reflux for 16 hr
3. temperatureThe reaction was cooled to room temperature
4. customquenched by the addition of saturated aqueous ammonium chloride
5. extractionThe reaction was extracted with ethyl acetate three times (100 mL)
6. washwashed with brine
7. dry with materialdried over magnesium sulfate
8. customevaporated in vacuo to a pale yellow oil
9. customThe oil was purified by flash chromatography (silica gel, hexane:ethyl acetate 9:1)

ORD record

ord-20bd31a95c61406db7414ae0f43ab512

Source dataset

uspto-grants-2007_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07230022B2