Reacción #162926

Ecuación de reacción

tert-butyl ((3S,7S,8R,9S)-7-benzyl-8-hydroxy-9-methyl-2-oxo−1,5-dioxonan-3-yl)carbamate

methyl propiolate

→

(E)-methyl 3-(((3S,6S,7R,8S)-8-benzyl-3-((tert-butoxycarbonyl)amino)-6-methyl-4-oxo-1,5-dioxonan-7-yl)oxy)acrylate

Rendimiento 91.2%

Disolventes

CH2Cl2

Condiciones de reacción

Tratamiento posterior

1. 1
   Concentraciónconcentrated
2. 2
   Otropurified by automated silica gel column chromatography (5-25% acetone in hexanes)

Procedimiento

To a solution of tert-butyl ((3S,7S,8R,9S)-7-benzyl-8-hydroxy-9-methyl-2-oxo−1,5-dioxonan-3-yl)carbamate (280 mg, 0.738 mmol, 1.00 equiv) in CH2Cl2 (7.4 mL) were added methyl propiolate (0.098 mL, 1.11 mmol, 1.50 equiv) and DABCO (4 mg, 0.04 mmol, 0.05 equiv). This solution was stirred at room temperature for 1 h, concentrated, and purified by automated silica gel column chromatography (5-25% acetone in hexanes) to provide (E)-methyl 3-(((3S,6S,7R,8S)-8-benzyl-3-((tert-butoxycarbonyl)amino)-6-methyl-4-oxo-1,5-dioxonan-7-yl)oxy)acrylate (312 mg, 91%) as a white solid: mp slow melt from 50-80° C., recrystallized at 98° C., remelt at 128-129° C.; IR (neat film) 3342, 2980, 2949, 1753, 1703, 1639, 1497, 1329, 1132, 910, 731 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.48 (d, J=12.2 Hz, 1H), 7.32-7.27 (m, 2H), 7.23-7.18 (m, 1H), 7.15-7.11 (m, 2H), 5.40 (d, J=12.2 Hz, 1H), 5.10 (d, J=8.3 Hz, 1H), 5.02 (dd, J=9.3, 6.4 Hz, 1H), 4.64 (dd, J=15.3, 7.5 Hz, 1H), 3.92 (dd, J=11.6, 7.6 Hz, 1H), 3.74 (d, J=9.1 Hz, 1H), 3.71 (s, 3H), 3.51 (d, J=11.1 Hz, 1H), 3.43 (dd, J=10.5, 6.4 Hz, 1H), 3.29 (dd, J=11.3, 7.5 Hz, 1H), 2.92 (dd, J=13.8, 3.5 Hz, 1H), 2.34 (t, J=12.5 Hz, 1H), 2.06 (s, 1H), 1.42 (s, 9H), 1.41 (d, J=6.5 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 172.16, 167.97, 162.94, 154.91, 138.54, 129.09, 128.57, 126.48, 98.50, 89.01, 80.31, 73.94, 72.57, 71.33, 52.70, 51.26, 46.47, 35.18, 28.25, 18.73; HRMS-ESI (m/z) [M+Na]+ calc'd for C24H33NO8Na, 486.2098. found, 486.2104.

Fuente