Ethyl Acetate → 1294481-80-3

Participants

Reaction Conditions

Reaction Steps

To a 1 liter dry round-bottomed flask was loaded ((2R,3R,4R)-3-(4-chlorobenzoyloxy)-4-fluoro-4-methyl-5-oxotetrahydrofuran-2-yl)methyl 4-chlorobenzoate (1b, 50.0 g, 113 mmol) and the solid was dissolved in anhydrous THF (200 mL). The solution was cooled to −20° C. Lithium tri-tert-butoxyaluminohydride (1.0 M in THF) (170 mL, 170 mmol) was added via an addition funnel over 20 min and the resulting mixture was stirred for an additional one hour at −20° C. Ethyl acetate (120 mL) was added and the mixture was allowed to warm up slowly to 0° C. Sat. aq ammonium chloride (4.5 mL) was added. The mixture was concentrated under reduced pressure and then diluted with EtOAc (500 mL). Aqueous HCl (3 N, 300 mL) was added to dissolve all solids. After separation, the organic layer was washed with water (2×200 mL), brine (100 mL), and dried over sodium sulfate. The organic layer was concentrated under reduced pressure to furnish an amorphous solid. The solid was dissolved in methanol (169 mL) heated to reflux. After cooling to room temperature, water was added portionwise (37 mL total) until a slightly turbid mixture formed. After standing, the precipitated β-lactol product was filtered and washed with methanol (2×20 mL) and dried (0.2 mmHg, 50° C., 17 h) to 30.5 g (61%) of an off-white solid with an anomeric ratio of β/α>35:1. 1H NMR (DMSO-d6): δ 7.95 (m, 2H, arom.), 7.90 (m, 2H, arom.), 7.61 (m, 2H, arom.), 7.51 (m, 2H, arom.), 7.31 (dd, 1H, C1-H, J=5.2 Hz, J=0.8 Hz), 5.50 (dd, 1H, C3-H, J=24 Hz, J=7.2 Hz), 5.19 (dd, 1H, C4-H, J=10.8 Hz, J=5.6 Hz), 4.56 (m, 1H, C5-Ha), 4.42 (m, 2H, C5-Hb and OH), 1.42 (d, 3H, CH3, J=22.8 Hz).

Provenance & Evidence