反应详情

温度

50 °C

To a clear solution of 4-[3-(4-bromo-2-methyl-phenylamino)-propyl]-tetrahydro-pyran-4-carboxylic acid methyl ester (0.85 g, 2.3 mmol) in THF (25 mL) was added NaH (60% in mineral oil, ˜100 mg) and the reaction temperature was raised to 50° C. (external) for 2 h. TLC (2.5% MeOH in DCM for SM, 5% MeOH in DCM for product) showed the reaction was complete. LC/MS detected the product peak. The reaction was cooled tin an ice-water bath, diluted with 25 mL of ethyl acetate, quenched with 10 mL of water. The two layers were separated. The aqueous layer was extracted with EtOAc (2×10 mL). The combined EtOAc extracts were washed with brine, and concentrated on rotavap to yield a crude product as a slightly yellow solid. This material was loaded onto a 25-g of silica gel column, eluted with DCM and 5% MeOH in DCM to get 0.81 g (95% yield) of the title compound as a white solid.

1. customquenched with 10 mL of water
2. customThe two layers were separated
3. extractionThe aqueous layer was extracted with EtOAc (2×10 mL)
4. washThe combined EtOAc extracts were washed with brine
5. concentrationconcentrated on rotavap
6. customto yield a crude product as a slightly yellow solid
7. washeluted with DCM and 5% MeOH in DCM