Diethyl benzylphosphonate → (E)-2-Bromo-4-styrylpyridine

To a solution of diethyl benzylphosphonate (4.57 mL, 21.91 mmol) in dimethylformamide (50 mL) at room temperature was added sodium methoxide (2.367 g, 43.8 mmol) and 18-Crown-6 (2.316 g, 8.76 mmol). After stirring at room temperature for 5 min, the reaction was cooled to 0° C. and treated with 2-bromoisonicotinaldehyde (4.89 g, 26.3 mmol) as a solid in one portion. The ice bath was removed and the reaction stirred at room temperature for 1 h. The reaction was gradually warmed to 120° C. and held there for 2 h. The reaction was cooled to room temperature and poured into water (500 mL) with vigorous stirring. The resulting suspension was extracted with diethyl ether (3×), washed with water, then brine, dried over magnesium sulfate, and concentrated to an oil. The resulting residue was purified by column chromatography (6% EtOAc/Hex-->12% EtOAc/Hex) to give 2.12 g (37%) as an oil. 1H-NMR (CDCl3, 500 MHz) δ 8.35 (d, J=5.2, 1H), 7.52-7.62 (m, 3H), 7.43 (m, 2H), 7.30-7.40 (m, 3H), 6.98 (d, J=16.2, 1H). 13C-NMR (CDCl3, 126 MHz) δ 150.4, 147.7, 143.1, 135.8, 134.8, 129.3, 129.0, 127.3, 125.0, 124.6, 120.1.

1. temperaturethe reaction was cooled to 0° C.
2. customThe ice bath was removed
3. stirringthe reaction stirred at room temperature for 1 h
4. temperatureThe reaction was gradually warmed to 120° C.
5. waitheld there for 2 h
6. temperatureThe reaction was cooled to room temperature
7. additionpoured into water (500 mL) with vigorous stirring
8. extractionThe resulting suspension was extracted with diethyl ether (3×)
9. washwashed with water
10. dry with materialbrine, dried over magnesium sulfate
11. concentrationconcentrated to an oil
12. customThe resulting residue was purified by column chromatography (6% EtOAc/Hex-->12% EtOAc/Hex)
13. customto give 2.12 g (37%) as an oil

ORD record

ord-f15e87100ace45d588d65936caa5d68f

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08691821B2