Diisopropylethylamine → 5-Chloro-2-{(S)-1-[(3R,4S)-4-(4-chloro-3-fluoro-phenyl)-pyrrolidin-3-yl]-ethoxy}-pyridine
Reaction equation
C([N:8]1[CH2:12][C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([F:20])[CH:14]=2)[C@@H:10]([C@@H:21]([O:23][C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][N:25]=2)[CH3:22])[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:30][C:27]1[CH:28]=[CH:29][C:24]([O:23][C@H:21]([C@@H:10]2[C@@H:11]([C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([F:20])[CH:14]=3)[CH2:12][NH:8][CH2:9]2)[CH3:22])=[N:25][CH:26]=1Participants
5
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 100 °C
Procedure
To a solution of 2-{(S)-1-[(3R,4S)-1-benzyl-4-(4-chloro-3-fluoro-phenyl)-pyrrolidin-3-yl]-ethoxy}-5-chloro-pyridine 98 mg (0.22 mmol) dissolved in toluene (5 mL) were added 0.072 mL (0.66 mmol) of 1-chloroethyl chloroformate and 0.11 mL (0.66 mL) 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 (5 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 75 mg (95%) of the title compound as a light yellow oil. ES-MS m/e: 355.1 (M+H+).
Workup
- temperatureAfter cooling down to RT
- customvolatiles were removed under vacuo
- dissolutionthe crude was dissolved in MeOH (5 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-2c521dcbf30f485f9900f52493ba408b
- Source dataset
- uspto-grants-2011_09
- Patent number
- US08012998B2
Reaction notes
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