反应详情

温度

-10 °C

A solution of [4-(2-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethoxy)-2-fluorophenyl]acetic acid (500 mg, 1.152 mmol) in 5 mL of THF cooled to −10° C. and TEA (0.177 mL, 1.268 mmol) was added. Methyl chloroformate (0.098 mL, 1.268 mmol) was added and the mixture stirred for 30 minutes at −10° C. The mixture was filtered and the filtercake washed with 10 mL THF. The filtrate was collected and concentrated under reduced pressure. The residue (265 mg, 0.539 mmol) was dissolved in 1 mL of DMF and hydrazine monohydrate (0.052 mL, 1.077 mmol) added. The mixture was stirred overnight at room temperature. The mixture was diluted with ethyl acetate (3 mL) and washed with water (2 mL) and brine (2 mL). The organics fractions were combined, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified using preparative TLC (1000 μM, silica gel) developing with 5% methanol in DCM. The band containing the product was collected and the silica washed with 10% methanol in DCM to elute the product. The solution was concentrated under reduced pressure to afford the title compound. HPLC/MS; 1.22 min(2 minute run), 448 (M+H)+.

1. filtrationThe mixture was filtered
2. washthe filtercake washed with 10 mL THF
3. customThe filtrate was collected
4. concentrationconcentrated under reduced pressure
5. stirringThe mixture was stirred overnight at room temperature
6. washwashed with water (2 mL) and brine (2 mL)
7. dry with materialdried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customThe residue was purified
11. additionThe band containing the product
12. customwas collected
13. washthe silica washed with 10% methanol in DCM
14. washto elute the product
15. concentrationThe solution was concentrated under reduced pressure