Thionyl Chloride → 3,5-Diisopropoxybenzoyl chloride

Participants

Reaction Steps

Diisopropoxybenzoic acid (compound F, 10 g, 41 mmol) was dissolved in benzene (100 mL) in a 500 mL round bottom flask. Thionyl chloride (12.2 mL, 168 mmol) was added and the reaction heated at reflux for 1 hour. The mixture was then cooled to room temperature and concentrated under reduced pressure. The resulting residue was redissolved in dichloromethane and concentrated again to give 3,5-diisopropoxybenzoyl chloride. In a separate 200 mL flask, N,O-dimethylhydroxylamine-HCl (4.0 g, 42 mmol) was suspended in 80 mL dichloromethane at 0° C. Triethylamine (12.4 mL, 88 mmol) was added slowly, followed by crude 3,5-diisopropoxybenzoyl chloride. The reaction flask was allowed to warm to ambient temperature and stirred overnight. The reaction was quenched with water and extracted with three portions of dichloromethane. The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. Purification of the resulting brown oil by column chromatography (30% acetone/hexane) gave the Weinreb amide (compound G) as a yellow oil in 60% yield from 3,5-dihydroxybenzoic acid: Rf 0.33 (30:70 acetone/hexane); IR (cm−1): 2977, 1647, 1590, 1441, 1374, 1184, 1155, 1113, 1037, 964; 1H NMR (250 MHz, C6D6): δ 1.06 (dd, J=2.5, 5.9 Hz, 12H), 3.00 (s, 3H), 3.05 (s, 3H), 4.19 (qn, J=6.2 Hz, 2H), 6.69 (t, J=2.5 Hz, 1H), 7.10 (d, J=2.5 Hz, 2H); 13C NMR (63 MHz, C6D6): 21.9 (4C), 33.4, 60.4, 69.8 (2C), 106.6, 108.1 (2C), 137.0, 159.3 (2C), 169.8.

Provenance & Evidence