Acetone → 6-bromo-2,2-dimethyl-3,4-dihydro-2H-1-benzopyran-4-one

Participants

Reaction Steps

To a solution of piperidine (2,83 g, 33.25 mmol) in 45 mL benzene was added trifluoroacetic acid (344.6 mg, 3.02 mmol) as a solution in 4.0 mL of benzene. Acetone (8.78 g, 151.3 mmol) was added followed by 2-hydroxy-5-bromoacetophenone (Compound 259, 6.50 g, 30.23 mmol). The resulting solution was heated to reflux in a flask fitted with a Dean-Stark trap. After 24 hours, an additional 2.5 equivalents of acetone and 0.1 equivalents of trifluoroacetic acid were added. After a total of 43 hours the reaction was cooled to room temperature and diluted with EtOAc. The solution was washed with 1M aqueous HCl, H2O, and saturated aqueous NaCl before being dried (MgSO4) and concentrated under reduced pressure. Distillation of the residual oil (bulb-to-bulb) afforded 4.80 g (62%) of the title compound as a clear yellow oil, bp 105-115° C./5 mm. The reaction conditions here are a moderate modification of the synthesis of the title compound described by Buckle et al. in J. Med. Chem. 1990 3028-3034. 1H NMR (300 MHz, CDCl3) δ: 7.97 (1H, d, J=2.6 Hz), 7.54 (1H, dd, J=2.6, 8.7 Hz), 6.84 (1H, d, J=8.8 Hz), 2.72 (2H, s), 1.46 (6H, s).

Provenance & Evidence