反应详情

温度

80 °C

Lithium diisopropyl amide (37.3 mmol) in THF (75 mL) at −78° C. was treated with 1-[3-(trifluoromethyl)pyridin-2-yl]piperidin-4-one (8.30 g, 34.0 mmol) in THF (25 mL) and stirred for 45 minutes. The mixture was treated with solid PhNTf2 (14.0 g, 39.1 mmol), stirred for 1 hour, and concentrated under reduced pressure. The residue was diluted with ethyl acetate:hexanes (1:1), washed with 1N NaOH, dried (Na2SO4), filtered through a silica plug, and the filtrate was concentrated under reduced pressure. The residue, triethylamine (14.2 mL, 102 mmol), and PdCl2(PPh3)2 (0.944 g, 1.34 mmol) were combined in methanol (7.00 mL, 173 mmol) and DMF (100 mL) and saturated with carbon monoxide gas (bubbling 15 minutes). The mixture was heated at 80° C. under a carbon monoxide atmosphere (1 atm) overnight. The mixture was concentrated to half volume, diluted with diethyl ether, washed with water, brine, dried (Na2SO4), filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography (6% ethyl acetate/hexanes) to provide the title compound.

1. stirringstirred for 1 hour
2. concentrationconcentrated under reduced pressure
3. additionThe residue was diluted with ethyl acetate:hexanes (1:1)
4. washwashed with 1N NaOH
5. dry with materialdried (Na2SO4)
6. filtrationfiltered through a silica plug
7. concentrationthe filtrate was concentrated under reduced pressure
8. concentrationThe mixture was concentrated to half volume
9. additiondiluted with diethyl ether
10. washwashed with water, brine
11. dry with materialdried (Na2SO4)
12. filtrationfiltered
13. concentrationthe filtrate was concentrated under reduced pressure
14. customThe residue was purified by flash chromatography (6% ethyl acetate/hexanes)