反应详情

温度

0 °C

To a solution of imidazole (252.3 g, 7.36 mol) in dry DMF (7.6 L) are added ethyl 3(S)-hydroxy-4-iodobutyrate (2) (949.6 g, 3.68 mol, GC purity 85.9%) and anhydrous NaI (1106 g, 7.36 mol) under argon atmosphere at ambient temperature. The suspension is cooled to 0° C. and tert-butyl(chloro)dimethylsilane (838 g, 5.56 mol) is added portionwise. The reaction mixture is stirred at 0° C. for 1.5 hours followed by stirring for 15.5 hours from 0° C. to ambient temperature. Then the mixture is cooled to 0° C. and H2O (4.2 L) is added. After 2 hours of stirring additional amount of H2O (6.2 L) and saturated Na2S2O3 solution (0.5 L) are added. The product is extracted with t-BuMeO. The combined organic layers are washed with water and dried (MgSO4). Ether is removed completely under the reduced pressure (20 mbar) at 60° C. to produce a yellow oily residue. This residue is purified further by vacuum distillation (80-89° C. at 0.150-0.310 mbar) to give 1193.5 g (97%) of ethyl 3(S)-(tert-butyldimethylsilyloxy)-4-iodobutyrate (3) as a pale yellow oil (GC purity 96.1%). 1H NMR (300 MHz, CDCl3): δ 4.13 (qd, J=7.2 and 2.1 Hz, 2H), 4.01 (m, 1H), 3.28 (dd, J=10.2 and 4.2 Hz, 1H), 3.24 (dd, J=10.2 and 6.0 Hz, 1H), 2.66 (dd, J=15.3 and 4.8 Hz, 1H), 2.51 (dd, J=15.3 and 7.2 Hz, 1H), 1.26 (t, J=7.2 Hz, 3H), 0.87 (s, 9H), 0.10 (s, 3H), 0.05 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 170.8, 68.3, 60.5, 42.5, 25.6, 17.9, 14.1, 12.9, −4.6, −5.0.

1. stirringby stirring for 15.5 hours from 0° C. to ambient temperature
2. temperatureThen the mixture is cooled to 0° C.
3. additionare added
4. extractionThe product is extracted with t-BuMeO
5. washThe combined organic layers are washed with water
6. dry with materialdried (MgSO4)
7. customEther is removed completely under the reduced pressure (20 mbar) at 60° C.
8. customto produce a yellow oily residue
9. distillationThis residue is purified further by vacuum distillation (80-89° C. at 0.150-0.310 mbar)