反应详情

To a 250 mL round bottle was added compound B1(I) ethyl 4-fluoropiperidine-4-carboxylate, hydrochloride (1.25 g, 5.91 mmol, 1.0 eq), CH2Cl2 (40 mL), cyclobutanone B1(II) (1.30 g, 7.68 mmol, 1.30 eq), and glacial HOAc (0.338 mL, 5.91 mmol, 1.0 eq). After stirring at rt for 5 to 10 min, sodium triacetoxyborohydride (2.00 g, 9.45 mmol, 1.60 eq) was added in one portion. A cloudy solution was obtained. The reaction mixture was stirred at rt for 2 h. To the reaction mixture, 100 mL aqueous NaOH (1 M) was added, and the resulting suspension was stirred at rt for 10 min. The reaction was extracted with EtOAc (150 mL). The organic layer was collected, washed with brine (200 mL), dried over Na2SO4, filtered, and concentrated to afford the desired product, B1(III), as a colorless oil. The crude product was cleaned and subjected to the next step without purification (see next step for the overall reaction yield). 1H NNR (400 MHz, CDCl3, ppm) δ 1.28 (t, J=7.20 Hz, 3H), 1.64-1.73 (m, 2H), 1.82-1.99 (m, 4H), 2.01-2.21 (m, 6H), 2.72-2.80 (m, 3H), 4.22 (q, J=7.2 Hz, 2H); 19F NMR (376 Hz, CDCl3, ppm) δ-166.83.

1. customA cloudy solution was obtained
2. stirringThe reaction mixture was stirred at rt for 2 h
3. stirringthe resulting suspension was stirred at rt for 10 min
4. extractionThe reaction was extracted with EtOAc (150 mL)
5. customThe organic layer was collected
6. washwashed with brine (200 mL)
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated