1,1-Dibromoethane → HCID 66727983, compound

Participants

Reaction Conditions

Reaction Steps

Cerium chloride (71.4 g, 290 mmoles) was slurried in tetrahydrofuran (600 mL) and heated to 65° C. for 2.5 hours, then cooled to room temperature In a separate flask, 4-bromobenzaldehyde diethylacetal (100 g, 386 mmoles) was dissolved in tetrahydrofuran (750 mL). Magnesium turnings (5.9 g, 241 mmoles) and dibromoethane (0.5 mL) were added and the mixture heated to reflux for 2.5 hours, until all the magnesium had reacted. Heating was removed and the Grignard solution cooled in an ice bath. The cerium chloride/tetrahydrofuran slurry was cooled in an ice bath to 0° C. The Grignard solution was added, portionwise, and the mixture stirred at 0° C. for 45 minutes. N-(t-butoxycarbonyl)azetidinone (41.3 g, 241 mmoles) dissolved in tetrahydrofuran (200 mL) was added portionwise and the reaction allowed to stir at 0° C. for 30 minutes. The reaction was quenched with saturated sodium carbonate solution (500 mL) and then diluted with ethyl acetate (2000 mL). The organic phase was washed with water (3×500 mL), separated, dried over anhydrous magnesium sulphate, filtered and evaporated to dryness to give a yellow oil weighing 120 g which was purified using normal phase chromatography (600 g SiO2 column, loaded as a solution in 25 mL of dichloromethane, linear gradient of 10% tert-butylmethylether in n-heptane to 100% tert-butylmethylether over 60 minutes, 150 mL/minutes, 55 mL fractions using the ‘Threshold OR Slope’ method) to give a light yellow oil weighing 65 g, which NMR suggests is the desired acetal product. 1HNMR (CDCl3) δ ppm: 7.50 (4H), 5.50 (1H), 4.15 (2H), 4.30 (2H), 3.55 (4H), 1.50 (9H), 1.25 (6H); m/z (ESI) 252 [M+H-Boc]+.

Provenance & Evidence