反应详情

温度

80 °C

To a vial containing 3-(4′,5′-difluoro-2′-methoxy-biphenyl-4-yloxymethyl)-phenylamine (0.35 g, 1.0 mmol) dissolved in acetonitrile (1 mL) was added bromo-acetic acid ethyl ester (0.113 ml, 1.0 mmol) and potassium carbonate (167 mg, 1.2 mmol) and additional acetonitrile (5 mL). The vial was sealed and heated to 80° C. overnight. The reaction was partitioned between ethyl acetate (200 mL) and aqueous HCl (0.1 M, 200 mL). The organic layer was separated and the aqueous layer extracted with ethyl acetate (200 mL). The organic layers were washed with brine (100 mL), combined, dried over magnesium sulfate, concentrated, dissolved in a minimal amount of dichloromethane and purified by flash chromatography with a 0-30% ethyl acetate in hexanes gradient to yield [3-(4′,5′-difluoro-2′-methoxy-biphenyl-4-yloxymethyl)-phenylamino]-acetic acid ethyl ester as a clear semisolid (190 mg, 44%). LC-MS (ES) calculated for C24H23F2NO4, 427.16; found m/z 428 [M+H]+.

1. customThe vial was sealed
2. customThe reaction was partitioned between ethyl acetate (200 mL) and aqueous HCl (0.1 M, 200 mL)
3. customThe organic layer was separated
4. extractionthe aqueous layer extracted with ethyl acetate (200 mL)
5. washThe organic layers were washed with brine (100 mL)
6. dry with materialdried over magnesium sulfate
7. concentrationconcentrated
8. dissolutiondissolved in a minimal amount of dichloromethane
9. custompurified by flash chromatography with a 0-30% ethyl acetate in hexanes gradient