反应详情

Methyl 2-[(4-{3-[ethyl(2-fluorobenzyl)amino]-3-oxopropyl}phenoxy)methyl]-benzoate (0.454 g, 1.001 mmol) was dissolved in EtOH (5 ml) and potassium hydroxide (0.085 g, 1.514 mmol) was added. The reaction was performed in a single node microwave oven (7 min, 150° C.). Workup was by removing the solvent by evaporation, addition of HCl (20 ml, 1 M) and the water phase was washed with two portions of EtOAc (20 ml). The organic phases were pooled 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 0.079 g of 2-[(4-{3-[ethyl(2-fluorobenzyl)amino]-3-oxopropyl}phenoxy)methyl]benzoic acid (18.0%).

1. customThe reaction was performed in a single node microwave oven
2. custom(7 min, 150° C.)
3. customby removing the solvent
4. customby evaporation, addition of HCl (20 ml, 1 M)
5. washthe water phase was washed with two portions of EtOAc (20 ml)
6. customthe solvent was removed by evaporation
7. customThe crude was purified by preparative HPLC (
8. concentrationthe acetonitrile concentration
9. temperaturewas increased to 100%
10. 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)
11. customthe acetonitrile was removed by evaporation
12. additionEtOAc (10 ml) was added
13. washthe organic phase was washed with two portions of brine
14. dry with materialdried (MgSO4)
15. customThe solvent was removed by evaporation