反应详情

温度

-15 °C

A mixture of 60 mg (0.20 mmol) of (3R)-3-[(1,1-dimethylethoxycarbonyl)amino]4-(2,5-difluorophenyl)butanoic acid and 0.033 mL (0.30 mmol) of N-methylmorpholine in 0.6 mL of THF was cooled to −15° C. and 0.031 mL of isobutyl chloroformate was added. After 10 min, 1.0 mL of ether was added. The mixture was transferred to a syringe and filtered through a syringe filter into a mixture of 35 mg (0.20 mmol) of amine hydrochloride from Step A and 0.033 mL (0.30 mmol) of N-methylmorpholine in 0.5 mL of THF at 0° C. The reaction mixture was warmed to ambient temperature. After 30 min, the reaction was judged to be complete by TLC. The mixture was filtered using a syringe filter, washing with ether, and concentrated under nitrogen. The solid was partitioned between ethyl acetate and water. The organics were washed with brine, dried over magnesium sulfate and concentrated to give a yellow oil. Purification by flash chromatography (5 g silica gel cartridge, 10 to 35% ethyl acetate/hexane step gradient) gave 62 mg (58%) of the title compound as a white solid.

1. customThe mixture was transferred to a syringe
2. filtrationfiltered through a syringe
3. temperatureThe reaction mixture was warmed to ambient temperature
4. waitAfter 30 min
5. filtrationThe mixture was filtered
6. filtrationfilter
7. washwashing with ether
8. concentrationconcentrated under nitrogen
9. customThe solid was partitioned between ethyl acetate and water
10. washThe organics were washed with brine
11. dry with materialdried over magnesium sulfate
12. concentrationconcentrated
13. customto give a yellow oil
14. customPurification by flash chromatography (5 g silica gel cartridge, 10 to 35% ethyl acetate/hexane step gradient)