反应详情

温度

19 °C

A 12-L three-neck round bottom flask with overhead mechanical stirrer, 2-L addition funnel and nitrogen inlet was charged the product of Example 1, Step A (1149 g, 2.875 mol, 1 eq) and THF (5.75 L). The addition funnel was charged with TBAF (1M solution in THF, 2.875 L, 2.875 mol, 1 eq) and this solution was added dropwise over ˜1 h. The temperature increased from 17 to 21° C. and the reaction was clear orange at the end. The reaction was stirred for 1 h at rt, when it was judged complete by TLC and HPLC. The reaction was poured into a 22-L separatory flask charged with EtOAc (4 L) and the organic layer was washed with brine (2 L). The organic layer was washed with additional brine (3×2 L) and these aqueous fractions were discarded. Heptane (4 L) was added and the organic layer was washed with water (3×2 L), brine (2×2 L) and the clear organic layer was checked by NMR for removal of n-Bu4NX. The organic layer was evaporated at 45° C. to about 750 mL, when the solution became hazy, heptane (800 mL) was added and instant crystallization of a white solid resulted. More heptane (300 mL) was added and the mixture was swirled at 40° C. for 10 min on the rotovap bath. Ice was added to bath and the suspension was stirred at 13° C. for 10 min. The solid was filtered on a Buchner funnel, washed with heptane (3×100 mL) and provided the product of Step A. 1H NMR (CHLOROFORM-d) δ: 6.02 (dd, J=5.4, 2.4 Hz, 1H), 5.77 (d, J=5.4 Hz, 1H), 5.21 (d, J=9.0 Hz, 1H), 4.91 (t, J=8.7 Hz, 1H), 4.37 (dd, J=7.5, 6.5 Hz, 2H), 2.21-2.39 (m, 3H), 2.07 (dd, J=13.8, 2.6 Hz, 1H), 1.44 (s, 9H). Calculated for C13H19NO4: 276.1 (M+23). found: 276.1.

1. additionthis solution was added dropwise over ˜1 h
2. additionThe reaction was poured into a 22-L separatory flask
3. washthe organic layer was washed with brine (2 L)
4. washThe organic layer was washed with additional brine (3×2 L)
5. additionHeptane (4 L) was added
6. washthe organic layer was washed with water (3×2 L), brine (2×2 L)
7. customthe clear organic layer was checked by NMR for removal of n-Bu4NX
8. customThe organic layer was evaporated at 45° C. to about 750 mL, when the solution
9. additionheptane (800 mL) was added
10. custominstant crystallization of a white solid
11. customresulted
12. waitthe mixture was swirled at 40° C. for 10 min on the rotovap bath
13. additionIce was added to bath
14. stirringthe suspension was stirred at 13° C. for 10 min
15. filtrationThe solid was filtered on a Buchner funnel
16. washwashed with heptane (3×100 mL)