Acetonitrile → Efinaconazole
Reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@:9]1([CH2:13][N:14]2[CH:18]=[N:17][CH:16]=[N:15]2)[C@H:11]([CH3:12])[O:10]1.[C:19](#[N:21])[CH3:20]>>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@:9]([OH:10])([C@H:11]([N:21]1[CH2:4][CH2:3][C:2](=[CH2:7])[CH2:20][CH2:19]1)[CH3:12])[CH2:13][N:14]1[CH:18]=[N:17][CH:16]=[N:15]1Participants
Conditions
- Temperature
- 100 °C
Procedure
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%).
Workup
- temperaturethe mixture was heated
- distillationethanol and distilled water
- additionwere added to the reaction mixture, whereupon a crystal
- customwas precipitated
- filtrationThereafter, the crystal was filtered off
- washwashed with 40 mL of an ethanol/water mixture
- customdried with air at room temperature
- customfurther dried under reduced pressure at 40° C. for 12 hours
Sources & evidence
- ORD record
- ord-1c949d4a2db146d892c62822d9539674
- Source dataset
- uspto-grants-2014_10
- Patent number
- US08871942B2
Reaction notes
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