反应详情

The methyl ester 13 (30 g, 95.8 mmol) was suspended in dry DCM (300 mL) with stirring in a round-bottomed flask equipped with a drying tube. Oxalyl chloride (13.4 g, 9.20 mL, 1.1 eq) was added followed by a few drops of DMF. The mixture was stirred overnight at room temperature. Triethylamine (21.3 g, 29.3 mL, 2.2 eq), +(S)-pyrrolidine methanol (9.68 g, 9.44 mL, 1.1 eq) were dissolved in dry DCM (150 mL) under nitrogen. The solution was cooled below −30° C. The acid chloride solution was added dropwise over 6 h maintaining the temperature below −30° C. It was then left to stir overnight at room temperature. The resulting solution was extracted with 1N HCl (2×200 mL), twice with water, once with brine. It was dried with magnesium sulfate and concentrated in vacuo to give a yellow/brown oil 14 which solidified on standing. (quantitative yield). It was used in the next step without further purification. 1H NMR (CDCl3) δ 7.70 (1H, s), 6.80 (1H, s), 4.40 (1H, m), 4.16 (2H, t, J=6.2 Hz), 3.97 (3H, s), 3.97-3.70 (2H, m), 3.71 (3H, s), 3.17 (2H, t, J=6.7 Hz), 2.57 (2H, t, J=7.1 Hz), 2.20 (2H, p, J=6.8 Hz), 1.90-1.70 (2H, m); 13C NMR (CDCl3) δ 173.2, 154.8, 148.4, 109.2, 108.4, 68.4, 66.1, 61.5, 56.7, 51.7, 49.5, 30.3, 28.4, 24.4, 24.2; IR (golden gate) vmax 3400, 2953, 1734, 1618, 1517, 1432, 1327, 1271, 1219, 1170, 1051, 995, 647 cm−1; MS (ES+) m/z (relative intensity) 397.07 ([M+H]+, 100); [α]24D=−84° (c=1, CHCl3).

1. customequipped with a drying tube
2. stirringThe mixture was stirred overnight at room temperature
3. temperatureThe solution was cooled below −30° C
4. temperaturemaintaining the temperature below −30° C
5. waitIt was then left
6. stirringto stir overnight at room temperature
7. extractionThe resulting solution was extracted with 1N HCl (2×200 mL), twice with water, once with brine
8. dry with materialIt was dried with magnesium sulfate
9. concentrationconcentrated in vacuo