Diisopropylethylamine → 2-{(S)-1-[(3R,4S)-4-(4-Chloro-phenyl)-pyrrolidin-3-yl]-ethoxy}-5-fluoro-pyridine
Reaction equation
C([N:8]1[CH2:12][C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=2)[C@@H:10]([C@@H:20]([O:22][C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][N:24]=2)[CH3:21])[CH2:9]1)C1C=CC=CC=1.ClC(OC(Cl)C)=O.CCN(C(C)C)C(C)C>C1(C)C=CC=CC=1>[Cl:19][C:16]1[CH:17]=[CH:18][C:13]([C@H:11]2[CH2:12][NH:8][CH2:9][C@@H:10]2[C@@H:20]([O:22][C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][N:24]=2)[CH3:21])=[CH:14][CH:15]=1Participants
5
Conditions
- Temperature
- 100 °C
Procedure
To a solution of 2-{(S)-1-[(3R,4S)-1-benzyl-4-(4-chloro-phenyl)-pyrrolidin-3-yl]-ethoxy}-5-fluoro-pyridine 310 mg (0.75 mmol) dissolved in toluene (5 mL) were added 0.10 mL (0.98 mmol) of 1-chloroethyl chloroformate and 0.17 mL (0.98 mmol) of Hunig's base. The reaction mixture was heated at 100° C. for one hour. After cooling down to RT, volatiles were removed under vacuo and the crude was dissolved in MeOH (10 mL). The reaction mixture was heated at 85° C. for 30 minutes and after cooling down to RT, volatiles were removed under vacuo and the residue was directly purified on column chromatography (SiO2, CH2Cl2/MeOH 9:1) yielded 230 mg (85%) of the title compound as a light yellow oil. ES-MS m/e: 321.3 (M+H+).
Workup
- temperatureAfter cooling down to RT
- customvolatiles were removed under vacuo
- dissolutionthe crude was dissolved in MeOH (10 mL)
- temperatureThe reaction mixture was heated at 85° C. for 30 minutes
- temperatureafter cooling down to RT
- customvolatiles were removed under vacuo
- customthe residue was directly purified on column chromatography (SiO2, CH2Cl2/MeOH 9:1)
Sources & evidence
- ORD record
- ord-93796c17419846ddbd3a489e8f8fc1e8
- Source dataset
- uspto-grants-2013_03
- Patent number
- US08394834B2
Reaction notes
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