反应详情

温度

2 °C

To a 5-L three-neck round bottom flask equipped with a mechanical stirrer, Claisen adapter with temperature probe and nitrogen inlet, and N2 outlet was purged with nitrogen for 2 h before use. The product of Step A (255.9 g, 1.01 mol, 1 eq) and MeOH (2 L) were added and the solution was chilled to 2° C. in an ice bath. NaBH4 (75 g, 1.98 mol, 2 eq) was added in ˜5 equal portions; the temperature exothermed to 17° C. before coming back to 6° C., when the next portion was added. The addition took ˜2.5 h and the reaction was judged complete by HPLC after the last addition. The reaction was quenched at 7° C. by addition of aqueous NH4Cl (saturated, 1 L), wherein the temperature rose to about 10° C. The white hazy mixture was concentrated on a rotary evaporate to about 1 L (45° C. bath) when a white solid with some liquid resulted. The mixture was diluted with water and EtOAc (1 L each), transferred to a separatory funnel and the layers were separated. The aqueous layer was extracted with EtOAc (3×250 mL). The combined organics were washed with brine (125 mL), dried over MgSO4, filtered through Celite and evaporated at a bath temperature of 55° C. and provided the product of Step B as a thick oil. 1H NMR (CHLOROFORM-d) δ: 5.74 (s, 2H), 4.65-4.95 (m, 2H), 3.70 (t, J=5.7 Hz, 2H), 3.40-3.57 (m, 2H), 2.76 (br. s., 1H), 2.28 (br. s., 1H), 2.19 (dd, J=13.4, 8.8 Hz, 1H), 1.70 (t, J=5.7 Hz, 2H), 1.55 (dd, J=13.8, 4.0 Hz, 1H), 1.44 (s, 9H). Calculated for C13H23NO4: 280.2 (M+23). found: 280.2.

1. customTo a 5-L three-neck round bottom flask equipped with a mechanical stirrer
2. customClaisen adapter with temperature probe and nitrogen inlet, and N2 outlet was purged with nitrogen for 2 h before use
3. customexothermed to 17° C.
4. custombefore coming back to 6° C.
5. additionwhen the next portion was added
6. additionThe addition
7. additionafter the last addition
8. customThe reaction was quenched at 7° C. by addition of aqueous NH4Cl (saturated, 1 L), wherein the temperature
9. customrose to about 10° C
10. concentrationThe white hazy mixture was concentrated on
11. customa rotary evaporate to about 1 L (45° C. bath) when a white solid with some liquid
12. customresulted
13. customtransferred to a separatory funnel
14. customthe layers were separated
15. extractionThe aqueous layer was extracted with EtOAc (3×250 mL)
16. washThe combined organics were washed with brine (125 mL)
17. dry with materialdried over MgSO4
18. filtrationfiltered through Celite
19. customevaporated at a bath temperature of 55° C.