18-Crown-6 → (E)-2-Bromo-6-(3-methoxystyryl)pyridine

To a solution of diethyl 3-methoxybenzylphosphonate (0.5 g, 1.94 mmol) in dimethylformamide (5 mL) at room temperature was added sodium methoxide (0.209 g, 3.87 mmol) and 18-Crown-6 (0.205 g, 0.77 mmol). After stirring at room temperature for 5 min, the reaction was cooled to 0° C. and treated with a solution of 6-bromopicolinaldehyde (0.432 g, 2.32 mmol) in dimethylformamide (2 mL) dropwise. When addition was complete, the ice bath was removed and the reaction stirred at room temperature for 1 h. The reaction was heated to 120° C. and held there for 2 h. The reaction was cooled to room temperature and stirred overnight. The resulting suspension was poured into water (70 mL) with vigorous stirring. The resulting suspension was extracted with diethyl ether (2×), washed with brine, dried over magnesium sulfate, and concentrated. The resulting residue was suspended in ethanol (ca. 10 ml). The resulting solution was placed in the freezer and held there for 3 h. The resulting precipitate was collected by filtration to give 150 mg (27%) as a white powder. 1H-NMR (CDCl3, 500 MHz) δ 7.61 (d, J=15.9, 1H), 7.49 (dd, J=7.6, 7.6, 1H), 7.22-7.36 (m, 3H), 7.16 (d, J=7.6, 1H), 7.10 (m, 1H), 7.07 (d, J=15.9, 1H), 6.87 (dd, J=8.2, 2.1, 1H), 3.84 (s, 3H). 13C-NMR (CDCl3, 126 MHz) δ 160.0, 157.1, 142.3, 138.9, 137.7, 134.4, 129.8, 126.7, 126.3, 120.7, 120.1, 114.8, 112.3, 55.4. Mass spec.: 290.01 (MH)+.

1. temperaturethe reaction was cooled to 0° C.
2. additionWhen addition
3. customthe ice bath was removed
4. stirringthe reaction stirred at room temperature for 1 h
5. temperatureThe reaction was heated to 120° C.
6. waitheld there for 2 h
7. temperatureThe reaction was cooled to room temperature
8. stirringstirred overnight
9. additionThe resulting suspension was poured into water (70 mL) with vigorous stirring
10. extractionThe resulting suspension was extracted with diethyl ether (2×)
11. washwashed with brine
12. dry with materialdried over magnesium sulfate
13. concentrationconcentrated
14. waitheld there for 3 h
15. filtrationThe resulting precipitate was collected by filtration
16. customto give 150 mg (27%) as a white powder

ORD record

ord-b4e71f5649d446c1bd183dc38b0eb5a6

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08691821B2