反应详情

Phosgene (3.5 mmol, 1.75 mL, 20% in toluene) was added to a solution of 34C (600 mg, 1.75 mmol) and NaHCO3 (1.47 g, 17.5 mmol) at 0° C. After stirring for 1 h at rt, the solution was filtered and concentrated in vacuo. 30B (375 mg, 1.75 mmol) in THF (20 mL) was added to the crude isocyanate and the solution was cooled to −45° C. NaH (93 mg) was added in one portion and the mixture was warmed to 0° C. and stirred for 2 h at 0° C. and 15 h at ambient temperature. Ammonium chloride (5 mL, saturated) was added and the reaction mixture was diluted with water and extracted with EtOAc. The organics were combined, washed with brine, dried over Na2SO4 and concentrated in vacuo. The crude product was purified by flash chromatography (0% to 50% EtOAc in hexanes) to yield 34D (578 mg, 57%) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ ppm 1.15 (t, J=7.15 Hz, 3 H) 2.32 (s, 3 H) 2.80-2.87 (m, J=6.87, 6.87 Hz, 2 H) 2.93 (t, J=7.15 Hz, 2 H) 4.05 (q, J=7.15 Hz, 2 H) 4.30 (t, J=7.15 Hz, 2 H) 5.02-5.18 (m, 3 H) 6.95-7.09 (m, 2 H) 7.23-7.37 (m, 10 H).

1. filtrationthe solution was filtered
2. concentrationconcentrated in vacuo
3. temperaturethe solution was cooled to −45° C
4. temperaturethe mixture was warmed to 0° C.
5. stirringstirred for 2 h at 0° C. and 15 h at ambient temperature
6. extractionextracted with EtOAc
7. washwashed with brine
8. dry with materialdried over Na2SO4
9. concentrationconcentrated in vacuo
10. customThe crude product was purified by flash chromatography (0% to 50% EtOAc in hexanes)