反应详情

温度

0 °C

A solution of (2S,5S)-tert-butyl 5-hydroxy-1-(2,2,2-trifluoroacetyl)piperidine-2-carboxylate (47.9 g, 161 mmol) in dehydrated acetonitrile (318 mL) was cooled to a temperature between −30 and −40° C. under an argon atmosphere, followed by adding 2,6-lutidine (20.5 mL), then adding dropwise trifluoromethanesulfonic anhydride (28.4 mL) over 40 minutes, and further allowing to react at −30° C. for 15 minutes. To this reaction mixture was added benzyloxyamine (39.7 g) (washed with acetonitrile (11 mL)) within 8 minutes, followed by raising the temperature to 0° C. within 30 minutes, further adding 2,6-lutidine (20.5 mL), and allowing to react at a temperature between 0 and 5° C. for 2 days. This reaction mixture was concentrated under reduced pressure, the resulting residue was diluted with ethyl acetate (960 mL), and washing with water (960 mL), 10% citric acid aqueous solution (960 mL× three times), 6.5% sodium bicarbonate aqueous solution (480 mL) and saturated brine (480 mL) sequentially. Each aqueous layer was back-extracted with ethyl acetate (960 mL), the organic layers were combined, and the solvent was distilled off under reduced pressure. The resulting residue was dissolved in 1,4-dioxane solution (320 mL) and water (86 mL), followed by adding dropwise 2.5M sodium hydroxide (128 mL) under ice-cooling, and allowing to react at the same temperature for 0.5 hours. To the reaction mixture was added acetic acid (approximately 9.3 mL), followed by concentrating under reduced pressure, the resulting concentrated residue was extracted with ethyl acetate (580 mL, 290 mL). Each organic layer was washed with 50% potassium carbonate aqueous solution (580 mL), followed by combining the organic layers and the solvent was distilled off under reduced pressure. The resulting residue was subjected to silica gel column chromatography (hexane/ethyl acetate=4/1→0/1 ethyl acetate/methanol=100/1→19/1) to afford 36.58 g of the title compound as a colorless oil (yield 74%). Instrumental data were consistent with those of Example 4.

1. customto react at −30° C. for 15 minutes
2. customto react at a temperature between 0 and 5° C. for 2 days
3. concentrationThis reaction mixture was concentrated under reduced pressure
4. additionthe resulting residue was diluted with ethyl acetate (960 mL)
5. washwashing with water (960 mL), 10% citric acid aqueous solution (960 mL× three times), 6.5% sodium bicarbonate aqueous solution (480 mL) and saturated brine (480 mL) sequentially
6. extractionEach aqueous layer was back-extracted with ethyl acetate (960 mL)
7. distillationthe solvent was distilled off under reduced pressure
8. dissolutionThe resulting residue was dissolved in 1,4-dioxane solution (320 mL)
9. additionby adding dropwise 2.5M sodium hydroxide (128 mL) under ice-
10. temperaturecooling
11. customto react at the same temperature for 0.5 hours
12. concentrationby concentrating under reduced pressure
13. extractionthe resulting concentrated residue was extracted with ethyl acetate (580 mL, 290 mL)
14. washEach organic layer was washed with 50% potassium carbonate aqueous solution (580 mL)
15. distillationthe solvent was distilled off under reduced pressure