反应详情

温度

-65 °C

A three-neck flask equipped with mechanical stirrer, thermometer, and nitrogen inlet was charged with 4-bromobenzaldehydediethyl acetal (800 g, 2.47 mol) and THF (7.2 L). The contents were cooled to −65° C. and treated with a 2.5M solution of n-BuLi in hexanes (1.23, 3.08 mol) at a rate to maintain temperature <−65° C. The solution was then treated with a solution of 9 (800 g, 2.47 mol) in THF (2.4 L) at a rate to maintain temperature <−65° C. The resulting solution was allowed to warm to ambient temperature over a 1 h period. At 20° C. the reaction was quenched by addition of a saturated aqueous NH4Cl solution (4 L) followed by EtOAc (4 L). After mixing well, the lower aqueous layer was separated and the organic layer washed with H2O (2×4 L). The organic layer was evaporated under reduced pressure to approximately 4 L. tert-BuOH (8 L) was added and evaporation continued to a volume of approximately 4 L. The solution was heated to 65° C. and treated with 3 N aqueous HCl (80 mL) and maintained at 65° C. for approximately 1 h. The reaction solution was diluted with heptane (8 L) and then cooled slowly to 5° C. and maintained for 1 h. The solids were collected by filtration, washed with heptane (2×1.5 L), and dried in vacuo at 40° C. to afford 511 g of 10 (63%) as a 98:2 mixture of Z:E isomers. 1HNMR (400 MHz, DMSO-d6): δ 0.83 (t, J=7.3 Hz, 3H), 2.33 (q, J=7.3 Hz, 2H), 6.41 (d, J=8.4 Hz, 2H), 6.60 (d, J=8.4 Hz, 2H), 7.10-7.20 (m, 5H), 7.40 (d, J=8.1 Hz, 2H), 7.90 (d, J=8.0 Hz, 2H), 9.25 (s, 1H), 9.98 (s, 1H).

1. customA three-neck flask equipped with mechanical stirrer
2. temperatureto maintain temperature <−65° C
3. temperatureto maintain temperature <−65° C
4. temperatureto warm to ambient temperature over a 1 h period
5. customAt 20° C. the reaction was quenched by addition of a saturated aqueous NH4Cl solution (4 L)
6. additionAfter mixing well
7. customthe lower aqueous layer was separated
8. washthe organic layer washed with H2O (2×4 L)
9. customThe organic layer was evaporated under reduced pressure to approximately 4 L
10. additiontert-BuOH (8 L) was added
11. customevaporation
12. temperatureThe solution was heated to 65° C.
13. additiontreated with 3 N aqueous HCl (80 mL)
14. temperaturemaintained at 65° C. for approximately 1 h
15. additionThe reaction solution was diluted with heptane (8 L)
16. temperaturecooled slowly to 5° C.
17. temperaturemaintained for 1 h
18. filtrationThe solids were collected by filtration
19. washwashed with heptane (2×1.5 L)
20. customdried in vacuo at 40° C.