反应详情

温度

75 °C

To a solution of 5F (3.0 g, 7.15 mmol) and 1-(2-ethoxy-2-oxoethyl)pyridinium bromide (1.189 g, 7.15 mmol) in EtOH (130 mL), was added ammonium acetate (11.03 g, 143 mmol) portion wise. After 15 min, the mixture was stirred at 75° C. The reaction mixture was then concentrated and dissolved in EtOAc. The organic layer was then washed with 1.0 N HCl, H2O, saturated sodium bicarbonate solution and finally by brine. The organic phase was dried over sodium sulfate, filtered and concentrated to yield a residue which was purified by normal phase chromatography to isolate 5G (2.2 g, 67%) as a brown solid. MS (ESI) m/z: 459.3 (M+H)+. The racemate was subjected to chiral separation using chiral AD-H 21×250 mm, eluting with a mixture of 35% (50/50 EtOH, i-PrOH and 0.1% DEA) and 65% CO2 with a flow rate of 70 mL/min and 150 bar at 40° C. to give enantiomer 5G1 (peak 1) and enantiomer 5G2 (peak 2).

1. concentrationThe reaction mixture was then concentrated
2. dissolutiondissolved in EtOAc
3. washThe organic layer was then washed with 1.0 N HCl, H2O, saturated sodium bicarbonate solution and finally by brine
4. dry with materialThe organic phase was dried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated
7. customto yield a residue which
8. customwas purified by normal phase chromatography