2,4-Dichlorobenzyl chloride → HCID 57810473, compound

Participants

Reaction Steps

To a solution of 3-(5-fluoro-3-methylindol-7-yl)acrylic acid, prepared as in Example 3 (20 g, 92 mmol) in 200 mL THF was added potassium t-butoxide (24.4 g, 206 mmol) in portions over approximately 10 min, while keeping the internal temperature below 18° C. with an ice-water bath. 2,4-Dichlorobenzyl chloride (21.7 g, 110 mmol) was added over a period of 5 min, after which the cooling bath was removed. The reaction mixture was stirred for 24 h, then quenched with 200 mL water, followed by dilution with 200 mL MTBE and 200 mL heptanes. After stirring for 10 min, the layers were separated, and the aqueous layer was filtered through a celite pad. The pad was rinsed with 50 mL water, and the aqueous filtrate was acidified to pH of 1-2 with 2 M HCl. The suspension was diluted with 200 mL MTBE and 100 mL heptanes, stirred for 5 min, then the solids were collected on a fritted glass funnel and rinsed with heptanes. The solids were dried under reduced pressure overnight at 58° C. to afford 24.4 g (70% yield) of the title compound: 1H-NMR (400 MHz, DMSO-d6) δ 2.26 (s, 3H), 5.55 (s, 2H), 6.21 (d, 1H, J=8.4 Hz), 6.24 (d, 1H, J=15.6 Hz), 7.22 (dd, 1H, J=10.4, 2.4 Hz), 7.28 (dd, 1H, J=8.6, 2.0 Hz), 7.34 (s, 1H), 7.43 (dd, 1H, J=8.6, 2.4 Hz), 7.66 (d, 1H, J=15.6 Hz), 7.67 (d, 1H, J=2.4 Hz), 12.29 (s, 1H).

Provenance & Evidence