反应详情

温度

55 °C

To a suspension of zinc dust (5.35 g, 82.3 mmol) in THF (10 mL) was added trimethylsilyl chloride (1.1 g, 10.15 mmol) at 40° C. The mixture was heated to 55° C. and stirred for 45 minutes. After cooling down to 37° C., ethyl bromoacetate (7.58 mL, 74.87 mmol) was slowly added to the reaction mixture at 37-40° C. After addition, the resulting mixture was allowed to cool to room temperature over 30 minutes. This solution was added to a solution of 2-methoxymethyl-4-(tetrahydro-pyran-2-yloxy)-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzaldehyde (1.99 g, 5.29 mmol) in THF (6 mL) at 0° C. The mixture was stirred for 10 minutes before treating with 3 N HCl and extracting with EtOAc (2×25 mL). The organic extracts were washed with brine, dried and concentrated in vacuo. The residue was purified by silica gel flash column chromatography and lyophilized to give (1,6-dihydroxy-4-methoxymethyl-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl)-acetic acid ethyl ester (1.0 g, 68%). 1H NMR (400 MHz, Acetone-d4) δ 8.40 (s, 1H), 8.00 (s, 1H), 7.10 (s, 1H), 6.90 (s, 1H), 5.60 (m, 1H), 4.47 (m, 2H), 4.08 (m, 2H), 3.37 (s, 3H), 3.10 9m, 1H), 2.25 (m, 1H), 1.20 (m, 3H).

1. temperatureAfter cooling down to 37° C.
2. additionAfter addition
3. temperatureto cool to room temperature over 30 minutes
4. stirringThe mixture was stirred for 10 minutes
5. extractionextracting with EtOAc (2×25 mL)
6. washThe organic extracts were washed with brine
7. customdried
8. concentrationconcentrated in vacuo
9. customThe residue was purified by silica gel flash column chromatography