反应详情

To a solution of 3-(4-fluorophenyl)-3-(4-bromophenyl)propionic acid* (1.0 g, 3.09 mmol) in acetone (4 ml) at 0° C. was sequentially added triethylamine (561 ul, 4.02 mmol) in acetone (1.6 ml) and ethyl chloroformate (443 ul, 4.64 mmol) in acetone (1.6 ml). The reaction was allowed to warm to room temperature, stirred for 30 minutes before cooling again to 0° C. and sodium azide (402 mg, 6.18 mmol) in water (1.6 ml) was added. The resultant brown solution was stirred for 45 minutes before addition of water (10 ml) and diethyl ether (10 ml). The aqueous layer was separated and extracted further with ethyl acetate (10 ml). The combined organic liquors were washed with saturated brine, dried (MgSO4) and concentrating in vacuo. The residue was dissolved in anhydrous toluene (12 ml) before addition of benzyl alcohol (567 ul, 9.27 mmol) and heating to 80° C. for 40 minutes. The reaction was allowed to cool to room temperature before addition of ethyl acetate (50 ml) and saturated sodium bicarbonate (50 ml). The organic liquors were separated and washed with further bicarbonate solution (50 ml), hydrochloric acid (2N, 100 ml) and saturated brine (50 ml) before drying (MgSO4) and concentrating in vacuo. The residue was purified by column chromatography (SiO2), eluting with ethyl acetate/petrol (5:95) gradient to (15:85) to afford the title compound (594 mg, 45%). LC/MS: (PS-A2) Rt 3.18 No Ionisation.

1. customat 0° C.
2. temperaturebefore cooling again to 0° C.
3. customThe aqueous layer was separated
4. extractionextracted further with ethyl acetate (10 ml)
5. washThe combined organic liquors were washed with saturated brine
6. dry with materialdried (MgSO4)
7. concentrationconcentrating in vacuo
8. temperatureheating to 80° C. for 40 minutes
9. customThe organic liquors were separated
10. washwashed with further bicarbonate solution (50 ml), hydrochloric acid (2N, 100 ml) and saturated brine (50 ml)
11. dry with materialbefore drying (MgSO4)
12. concentrationconcentrating in vacuo
13. customThe residue was purified by column chromatography (SiO2)
14. washeluting with ethyl acetate/petrol (5:95) gradient to (15:85)