反应详情

温度

65 °C

N-Ethyl-N-(2-fluorobenzyl)-3-(4-hydroxyphenyl)propanamide (0.400 g, 1.327 mmol) and methyl 2-(bromomethyl)benzoate (0.334 g, 1.460 mmol) were dissolved in acetonitrile (10 ml) and potassium carbonate (0.367 g, 2.654 mmol) was added. The mixture was stirred at 65° C. for three hours. When N-ethyl-N-(2-fluorobenzyl)-2-(4-hydroxyphenyl)acetamide was consumed, PS-trisamine (0.3 eqv) was added and the solution was stirred overnight at room temperature. The polymer was filtered off and acetonitrile was removed by evaporation. EtOAc (10 ml) was added and the organic phase was washed with two portions of water, dried (MgSO4) and the solvent was removed by evaporation. EtOAc (10 ml) was added and the organic phase was washed with two portions on water, dried (MgSO4) and the solvent was removed by evaporation. The crude was purified by preparative HPLC (starting with isocratic 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 were pooled and the acetonitrile was removed by evaporation. EtOAc (10 ml) was added and the organic phase was washed with two portions of brine and dried (MgSO4). The solvent was removed by evaporation. to give 0.454 g of methyl 2-[(4-{3-[ethyl(2-fluorobenzyl)amino]-3-oxopropyl}phenoxy)methyl]-benzoate (yield 76.1%).

1. customWhen N-ethyl-N-(2-fluorobenzyl)-2-(4-hydroxyphenyl)acetamide was consumed
2. stirringthe solution was stirred overnight at room temperature
3. filtrationThe polymer was filtered off
4. customacetonitrile was removed by evaporation
5. additionEtOAc (10 ml) was added
6. washthe organic phase was washed with two portions of water
7. dry with materialdried (MgSO4)
8. customthe solvent was removed by evaporation
9. additionEtOAc (10 ml) was added
10. washthe organic phase was washed with two portions on water
11. dry with materialdried (MgSO4)
12. customthe solvent was removed by evaporation
13. customThe crude was purified by preparative HPLC (
14. concentrationthe acetonitrile concentration
15. temperaturewas increased to 100%
16. 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)
17. customthe acetonitrile was removed by evaporation
18. additionEtOAc (10 ml) was added
19. washthe organic phase was washed with two portions of brine
20. dry with materialdried (MgSO4)
21. customThe solvent was removed by evaporation