Water → ethyl (R)-6-(3-(2-ethoxyphenoxy)piperidin-1-yl)nicotinate
Reaction equation
C(N(CC)CC)C.[CH2:8]([O:10][C:11]1[CH:23]=[CH:22][CH:21]=[CH:20][C:12]=1[O:13][C@@H:14]1[CH2:19][CH2:18][CH2:17][NH:16][CH2:15]1)[CH3:9].Cl[C:25]1[CH:35]=[CH:34][C:28]([C:29]([O:31][CH2:32][CH3:33])=[O:30])=[CH:27][N:26]=1.O>C(#N)C>[CH2:8]([O:10][C:11]1[CH:23]=[CH:22][CH:21]=[CH:20][C:12]=1[O:13][C@@H:14]1[CH2:19][CH2:18][CH2:17][N:16]([C:25]2[CH:35]=[CH:34][C:28]([C:29]([O:31][CH2:32][CH3:33])=[O:30])=[CH:27][N:26]=2)[CH2:15]1)[CH3:9]Participants
6
Conditions
- Temperature
- 90 °C
Procedure
Triethylamine (8.1 mL, 80 mmol) was added to a stirred solution of (R)-3-(2-ethoxy-phenoxy)-piperidine (10 g, 39 mmol) and ethyl 6-chloronicotinate (7.2 ml, 39 mmol) in acetonitrile (100 mL) at 0° C. The reaction mixture was heated at 90° C. for 16 h. The mixture was cooled to ambient temperature, water (150 mL) was added, and the mixture was extracted with ethyl acetate (3×200 mL). The combined organic layers were washed sequentially with water (100 mL) and brine (100 mL), then were dried over sodium sulfate, filtered and concentrated. The crude material was purified by column chromatography (13% ethyl acetate-hexanes) to afford ethyl (R)-6-(3-(2-ethoxyphenoxy)piperidin-1-yl)nicotinate (8.8 g). MS (ES+) 371.0 (M+H).
Workup
- temperatureThe mixture was cooled to ambient temperature
- extractionthe mixture was extracted with ethyl acetate (3×200 mL)
- washThe combined organic layers were washed sequentially with water (100 mL) and brine (100 mL)
- dry with materialwere dried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated
- customThe crude material was purified by column chromatography (13% ethyl acetate-hexanes)
Sources & evidence
- ORD record
- ord-dcb5fc26fcd64ba39881d0c8a6b4c026
- Source dataset
- uspto-grants-2016_09
- Patent number
- US09440949B2
Reaction notes
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