反应详情

温度

60 °C

To a stirred solution of methyl 3-amino-5-fluoro-2-methylbenzoate (520 mg, 2.84 mmol) in THF (20 mL) and TFA (813 uL) was added (2R,6S)-1-benzyl-2,6-dimethylpiperidin-4-one (679 mg, 3.12 mmol) at 0° C. The mixture was stirred at 60° C. for 1 hour under nitrogen atmosphere. Then the mixture was cooled to 0° C. in an ice bath, sodium triacetoxyborohydride (1.27 g, 5.68 mmol) was added. The reaction mixture was stirred at rt for 2 hours. Then aq. NaHCO3 was added at 0° C. until pH8-9, and the content was extracted with ethylacetate. The organic layer was dried over MgSO4 and filtered. The filtrate was concentrated in vacuo. The residue was purified by silica gel column chromatography (NH—SiO2; heptane/ethylacetate=5/1) to give titled compound as a colorless oil (331 mg, 30% yield.). 1H-NMR (400 MHz, CDCl3) δppm; 7.35-7.39 (m, 2H), 7.27-7.30 (m, 2H), 7.21-7.26 (m, 1H), 6.76 (dd, J=2.4, 9.2 Hz, 1H), 6.45 (dd, J=2.4, 11.2 Hz, 1H), 3.94 (d, J=14.4 Hz, 1H), 3.87 (s, 3H), 3.58-3.65 (m, 2H), 3.46 (d, J=14.4 Hz, 1H), 3.06-3.12 (m, 1H), 2.94-3.01 (m, 1H), 2.21 (s, 3H), 2.02-2.07 (m, 1H), 1.82-1.89 (m, 1H), 1.15-1.22 (m, 1H), 1.12 (d, J=6.0 Hz, 3H), 1.09 (d, J=7.2 Hz, 3H).

1. temperatureThen the mixture was cooled to 0° C. in an ice bath
2. stirringThe reaction mixture was stirred at rt for 2 hours
3. extractionthe content was extracted with ethylacetate
4. dry with materialThe organic layer was dried over MgSO4
5. filtrationfiltered
6. concentrationThe filtrate was concentrated in vacuo
7. customThe residue was purified by silica gel column chromatography (NH—SiO2; heptane/ethylacetate=5/1)