반응 #628211

반응 방정식

(2R,3S)-2-(2,4-difluorophenyl)-3-methyl-2-[(1H-1,2,4-triazol-1-yl)methyl]oxirane

acetonitrile

→

KP-103

(2R,3R)-2-(2,4-difluorophenyl)-3-(4-methylenepiperidin-1-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol

반응 조건

후처리

1. 1
   온도the mixture was heated
2. 2
   workup.DISTILLATIONethanol and distilled water
3. 3
   workup.ADDITIONwere added to the reaction mixture, whereupon a crystal
4. 4
   기타was precipitated
5. 5
   여과Thereafter, the crystal was filtered off
6. 6
   세척washed with 40 mL of an ethanol/water mixture
7. 7
   기타dried with air at room temperature
8. 8
   기타further dried under reduced pressure at 40° C. for 12 hours

실험 절차

21.26 g (119.4 mmol) of the 4-methylenepiperidine hydrobromide (4-MP.HBr) obtained in Production 1 and 2.859 g (119.4 mmol) of lithium hydroxide were added to 80 mL of acetonitrile and stirred for a while. Thereafter, 20 g (79.6 mmol) of (2R,3S)-2-(2,4-difluorophenyl)-3-methyl-2-[(1H-1,2,4-triazol-1-yl)methyl]oxirane was added and the mixture was heated under reflux in an oil bath (external temperature: 100° C.) for 14 hours. After the reaction completed, ethanol and distilled water were added to the reaction mixture, whereupon a crystal was precipitated. Thereafter, the crystal was filtered off, washed with 40 mL of an ethanol/water mixture, dried with air at room temperature and further dried under reduced pressure at 40° C. for 12 hours to give a pale yellow crystal of KP-103 in an amount of 24.2 g (yield, 87.3%; purity on HPLC, 95.3%).

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