Oxalyl chloride → (S)-4-(4-fluoro-phenyl)-6-oxo-1,4,5,6-tetrahydro-pyridine-3-carboxylic acid chloride
Reaction equation
[C:1](Cl)(=O)[C:2]([Cl:4])=[O:3].[F:7][C:8]1[CH:13]=[CH:12][C:11]([C@@H:14]2[CH2:19][C:18](=[O:20])[NH:17][CH:16]=C2C(O)=O)=[CH:10][CH:9]=1>ClCCl.CN(C=O)C>[F:7][C:8]1[CH:9]=[CH:10][C:11]([C@@H:14]2[CH2:19][C:18](=[O:20])[NH:17][CH:16]=[C:1]2[C:2]([Cl:4])=[O:3])=[CH:12][CH:13]=1Participants
Procedure
Oxalylchloride (0.91 g 7.2 mmol) was added to a room temperature solution of (S)-4-(4-fluoro-phenyl)-6-oxo-1,4,5,6-tetrahydro-pyridine-3-carboxylic acid (1.124 g, 4.8 mmol) in dichloromethane (10 ml) containing 2 drops of DMF. The reaction mixture was stirred for 30 minutes and then solvent was removed under reduced pressure to give crude (S)-4-(4-fluoro-phenyl)-6-oxo-1,4,5,6-tetrahydro-pyridine-3-carboxylic acid chloride, which was not removed from the flask. Dichloromethane (10 mL) was added, and the dichloromethane solution of the acid chloride was added to a stirring solution of 5-[2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-4-chloro-2-methyl-phenylamine (1.51 g, 4.7 mmol) and triethyl amine (0.97 g) in dichloromethane (30 ml). The reaction was stirred at 0° C. for 10 minutes, then at ambient temperature for 20 minutes. Solvent was removed under reduced pressure and the residue was purified by flash chromatography (0 to 5% methanol in dichloromethane) to 1.776 g of (S)-4-(4-fluoro-phenyl)-6-oxo-1,4,5,6-tetrahydro-pyridine-3-carboxylic acid {5-[2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-4-chloro-2-methyl-phenyl}-amide as a yellowish solid (69.5% yield).
Workup
- customsolvent was removed under reduced pressure
Sources & evidence
- ORD record
- ord-dae35da40e6a48aaa38eab77c81ee607
- Source dataset
- uspto-grants-2012_10
- Patent number
- US08288552B2
Reaction notes
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