4-Chlorophenyl Isocyanate → 3-(N-tert-Butoxycarbonylamino)-N-(4-chlorophenyl)-pyridine-4-carboxamide
Reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Li]C(C)(C)C.[Cl:20][C:21]1[CH:26]=[CH:25][C:24]([N:27]=[C:28]=[O:29])=[CH:23][CH:22]=1>C1COCC1>[C:1]([O:5][C:6]([NH:8][C:9]1[CH:10]=[N:11][CH:12]=[CH:13][C:14]=1[C:28]([NH:27][C:24]1[CH:25]=[CH:26][C:21]([Cl:20])=[CH:22][CH:23]=1)=[O:29])=[O:7])([CH3:4])([CH3:2])[CH3:3]Participants
Conditions
- Temperature
- -30 °C
Procedure
The 3-tert-butoxycarbonylaminopyridine (2.0035 g, 10.32 mmol) was dissolved in THF (100 mL). The solution was cooled to −30° C. in a dry ice/acetonitrile bath, then t-BuLi (13 mL, 22.1 mmol) was added dropwise. After 1 h, 4-chlorophenyl isocyanate (1.911 g, 12.44 mmol) was added. The reaction mixture was warmed to 0° C. After 1.5 h, the reaction was warmed to room temperature. After 3 h at room temperature, the reaction was quenched with water (100 mL) and extracted with EtOAc (800 mL). The organic layer was washed with water (2×50 mL), dried over sodium sulfate, filtered, and concentrated. The crude material was purified by flash column chromatography (350 g silica, 30% EtOAc/-CH2Cl2) to give the amide (1.284 g, 3.69 mmol, 36%) as a pale yellow solid.
Workup
- temperatureThe reaction mixture was warmed to 0° C
- waitAfter 1.5 h
- temperaturethe reaction was warmed to room temperature
- waitAfter 3 h at room temperature
- customthe reaction was quenched with water (100 mL)
- extractionextracted with EtOAc (800 mL)
- washThe organic layer was washed with water (2×50 mL)
- dry with materialdried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated
- customThe crude material was purified by flash column chromatography (350 g silica, 30% EtOAc/-CH2Cl2)
Sources & evidence
- ORD record
- ord-a2f5b3af7a1a425d85bfd0a6f9b274fa
- Source dataset
- uspto-grants-2009_03
- Patent number
- US07511066B2
Reaction notes
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