1-Bromo-4-(diethoxymethyl)benzene → 4-[(1Z)-1-(4-Hydroxyphenyl)-2-phenylbut-1-enyl]benzaldehyde

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Reaction Conditions

Reaction Steps

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).

Provenance & Evidence