反应详情

Added 13.84 g Na2CO3 to a 500 ml three neck round bottom flask equipped with a mechanical stirrer, addition funnel, and thermocouple. Then added 86 ml water and stirred until full dissolution at room temperature. 20 g 3-nitrobenzylamine HCl 2b was then added, followed by 154 ml toluene. The mixture was heated to 50° C. wherein a clear biphasic solution results. Added a 20% w/w solution of (S)-tetrahydrofuran-3-yl chloroformate, 2a (16 g) in toluene (80 ml) dropwise over 45 minutes wherein very little exotherm was noted. The reaction mixture was stirred for an additional 1 hour before the layers were separated at 50° C. The mixture was concentrated to ˜85 ml, cooled to 0° C. and stirred for 1 hour at 0° C. Precipitated product was collected by filtration and dried for 18 hours at 53° C. to give 26.64 g (94.4% yield, 99.90% a/a) of (S)-tetrahydrofuran-3-yl 3-nitrobenzylcarbamate (2c) as a white crystalline solid with consistent 1H NMR (500 MHz, d6-DMSO): 8.10 (m, 2H); 7.90 (m, 1H); 7.70 (d, 1H); 7.62 (t, 1H); 5.10 (br, 1H); 4.30 (d, 2H); 3.72 (m, 4H); 2.10 (m, 1H); 1.87 (m, 1H)ppm.

1. customequipped with a mechanical stirrer, addition funnel
2. temperatureThe mixture was heated to 50° C. wherein a clear biphasic solution
3. customresults
4. stirringThe reaction mixture was stirred for an additional 1 hour before the layers
5. customwere separated at 50° C
6. concentrationThe mixture was concentrated to ˜85 ml
7. temperaturecooled to 0° C.
8. stirringstirred for 1 hour at 0° C
9. filtrationPrecipitated product was collected by filtration
10. customdried for 18 hours at 53° C.