反应详情

A solution of 2e-1 (173.6 mg, 0.54 mmol) in THF (Sure/Seal solvent redried over 3-- MS, 1.45 mL) is added to excess cold phosgene (1.92M solution in toluene; 1.40 mL, 2.63 mmol), alternately with TEA (81 μl, 0.58 mmol) over a period of 15 min at 0° C. The resulting milky mixture is stirred for an addition 15 min at the same temperature and for 5 h at room temperature. The mixture is degassed with argon for 30 min and stirred under aspirator pressure for 30 min. The residue is treated with a solution of freshly prepared 3b (0.37 mmol) in CH3CN (redried as for THF, 2.9 mL) and then TEA (81 μl, 0.58 mmol), both added all at once. The white slurry is stirred overnight at ambient temperature. The mixture is taken up in EtOAc/H2O and the layers separated. The aq. phase is extracted with EtOAc twice and the combined organic phase is washed with brine, dried, filtered, and evaporated. Purification of the product by chromatography (3×30 cm column, gradient of 2:1-1:2 hexane/EtOAc) gaves a white wax which is identified as 1a-1: NMR δ 0.86 (m, 3 H), 1.11 (d, J=6.4, 3 H), 1.20-1.40 (m, 8 H), 1.42 (d, J=7.3, 3 H), 1.50-1.75 (m, 4 H, with overlapping H2O signal), 1.75-2.05 (br d, 2 H), 2.20 (m, 2 H), 4.15 (br s, 1 H), 4.47 (br s, 1 H), 4.62 (apparent quintet, 1 H), 4.87 (apparent br d, J≈6, 1 H), 5.00-5.20 (m, 9 H), 5.23 (m, 1 H), 5.37 (br d, 1 H), 6.40 (br d, 1 H), 7.33 (m, 20 H), 7.77 (br d, 1 H); MS (HR-FAB) m/z 923.4420 (M+H, calcd. for C51H63N4O12, 923.4442).

1. customThe mixture is degassed with argon for 30 min
2. stirringstirred under aspirator pressure for 30 min
3. additionThe residue is treated with a solution
4. stirringThe white slurry is stirred overnight at ambient temperature
5. customthe layers separated
6. extractionThe aq. phase is extracted with EtOAc twice
7. washthe combined organic phase is washed with brine
8. customdried
9. filtrationfiltered
10. customevaporated
11. customPurification of the product by chromatography (3×30 cm column, gradient of 2:1-1:2 hexane/EtOAc)