反应详情

温度

-78 °C

A three-necked RBF equipped with nitrogen inlet tube and dry ice condenser was charged with (3R,5R,6S)-tert-butyl 3-allyl-2-oxo-5,6-diphenyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butyl)morpholine-4-carboxylate (4.60 g, 8.00 mmol) and THF (10 mL). After cooling the condenser to −78° C. and the flask to −45° C. (CO2 (s), CH3CN), ammonia (80 mL) was condensed into the flask. Once complete, lithium metal (0.55 g, 80 mmol, small pieces) was carefully added over 10 min. After stirring an additional 40 min, the reaction mixture was carefully quenched with NH4Cl (s) until the solution became clear. The bath was removed and the ammonia was allowed to evaporate over night. The resulting residue was diluted with ethyl acetate and washed successively with 0.5N HCl and saturated aqueous NaCl, dried over MgSO4, filtered and concentrated. The crude product was dissolved in 50% methanol in toluene (80 mL, 0.1 M) and treated with TMSCHN2 (2.0 M in hexanes) until the pale yellow color persisted. With TLC indicating the reaction complete, the excess TMSCHN2 was quenched with acetic acid until the solution became clear. The solution was concentrated, diluted with ethyl acetate and washed successively with saturated aqueous NaHCO3 and saturated aqueous NaCl, dried over MgSO4, filtered and concentrated. Purification by MPLC (1-60% ethyl acetate in heptane over 6 CV) gave (R)-methyl 2-allyl-2-(tert-butoxycarbonylamino)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)hexanoate as colorless oil (1.9 g, 58%). Rf 0.46 (30% ethyl acetate in heptane); 1H NMR (CDCl3, 300 MHz) δ 5.70-5.52 (m, 1H), 5.49-5.36 (m, 1H), 5.05 (dd, J1=13.8 Hz, J2=1.2 Hz, 1H), 3.73 (s, 3H), 3.09-2.96 (m, 1H), 2.50 (dd, J1=13.8 Hz, J2=7.8 Hz, 1H), 2.29-2.10 (m, 1H), 1.78-1.65 (m, 1H), 1.43 (s, 9H), 1.42-1.26 (m, 4H), 1.23 (s, 12H), 0.74 (t, J=7.5 Hz, 2H); ESI-LCMS m/z calcd for C21H38BNO6: expected 411.3. found 412.3 (M+H)+.

1. customA three-necked RBF equipped with nitrogen inlet tube and dry ice condenser
2. customto −45° C.
3. customcondensed into the flask
4. customthe reaction mixture was carefully quenched with NH4Cl (s) until the solution
5. customThe bath was removed
6. customto evaporate over night
7. additionThe resulting residue was diluted with ethyl acetate
8. washwashed successively with 0.5N HCl and saturated aqueous NaCl
9. dry with materialdried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated
12. dissolutionThe crude product was dissolved in 50% methanol in toluene (80 mL, 0.1 M)
13. additiontreated with TMSCHN2 (2.0 M in hexanes) until the pale yellow color
14. customthe reaction complete
15. customthe excess TMSCHN2 was quenched with acetic acid until the solution
16. concentrationThe solution was concentrated
17. additiondiluted with ethyl acetate
18. washwashed successively with saturated aqueous NaHCO3 and saturated aqueous NaCl
19. dry with materialdried over MgSO4
20. filtrationfiltered
21. concentrationconcentrated
22. customPurification by MPLC (1-60% ethyl acetate in heptane over 6 CV)