反应详情

To a solution of 3-[4-(tert-butyl-dimethyl-silanyloxymethyl)-phenyl]-2-[2-(4-fluoro-phenyl)-ethylsulfanyl]-propionic acid (4.79 g, 10.68 mmol) and 2,2,2-trichloroethanol (1.67 g, 11.22 mmol) in anhydrous DCM (300 mL) was first added EDCxHCl (2.66 g, 13.89 mmol) then DMAP (13 mg, 0.1 mmol) under nitrogen atmosphere at 0° C. After complete addition the cooling bath was removed and the reaction mixture was stirred at ambient temperature until no starting material was left. The mixture was diluted with water and aq. HCl (2N) and extracted with DCM. The combined organic layers were dried (MgSO4) and the solvent was evaporated under reduced pressure to afford the crude product which was directly proceeded to the next step (5.47 g, 88.3%). 1H NMR (400 MHz, CDCl3): δ 7.16 (t, 2H), 7.10 (d, 2H), 7.01 (t, 2H), 6.87 (t, 2H), 4.61 (q, 4H), 3.48 (dd, 1H), 3.12 (dd, 1H), 2.73-2.89 (m, 5H), 0.85 (s, 9H), 0.00 (s, 6H). Mass Spectrum: M−H+ 579.03.

1. customat 0° C
2. additionAfter complete addition the cooling bath
3. customwas removed
4. waitwas left
5. additionThe mixture was diluted with water and aq. HCl (2N)
6. extractionextracted with DCM
7. dry with materialThe combined organic layers were dried (MgSO4)
8. customthe solvent was evaporated under reduced pressure