反应详情

温度

0 °C

3-(4-Mercaptophenyl)propanoic acid (2.0 g, 10.97 mmol) was dissolved in dry THF (60 ml) and cooled to 0° C. Sodium hydride (0.64 g, 24.1 mmol) was added. The mixture was stirred for 30 minutes, methyl 2-(bromomethyl)benzoate (2.77 g, 12.07 mmol) dissolved in dry THF (10 ml) was added dropwise. The solution was allowed to warm up to room temperature and was stirred overnight. Dropwise addition of water (10 ml) deactivated the remaining sodium hydride. The solvent was removed by evaporation, and the residue was acidified to pH 3 (HCl 1%). The water phase was washed with EtOAc (3×10 ml). The organic phases was combined, dried (MgSO4) and evaporated. The crude was purified by preparative HPLC (started with acetonitrile/buffer 60/40 and then the acetonitrile concentration was increased to 100%, the buffer was a mixture of acetonitrile/water 10/90 and ammonium acetate (0.1 M, column KR-100-7-C8, 50 mm×250 mm, flow 40 ml/min). The product containing fractions was pooled and the acetonitrile was removed by evaporation. EtOAc (10 ml) was added and the organic phase was washed with two potions of brine and dried (MgSO4). Removing the solvent by evaporation gave 2.26 gram of 3-(4-{[2-(methoxycarbonyl)benzyl]thio}phenyl)propanoic acid (yield 62.3%).

1. additionwas added dropwise
2. temperatureto warm up to room temperature
3. stirringwas stirred overnight
4. customThe solvent was removed by evaporation
5. washThe water phase was washed with EtOAc (3×10 ml)
6. dry with materialdried (MgSO4)
7. customevaporated
8. customThe crude was purified by preparative HPLC (
9. concentrationthe acetonitrile concentration
10. temperaturewas increased to 100%
11. additiona mixture of acetonitrile/water 10/90 and ammonium acetate (0.1 M, column KR-100-7-C8, 50 mm×250 mm, flow 40 ml/min)
12. additionThe product containing fractions
13. customthe acetonitrile was removed by evaporation
14. additionEtOAc (10 ml) was added
15. washthe organic phase was washed with two potions of brine
16. dry with materialdried (MgSO4)
17. customRemoving the solvent
18. customby evaporation