Isoguvacine → 1-(3-chloropyridin-2-yl)-1,2,3,6-tetrahydropyridine-4-carboxylic Acid
Reaction equation
[NH:1]1[CH2:6][CH:5]=[C:4]([C:7]([OH:9])=[O:8])[CH2:3][CH2:2]1.Br[C:11]1[C:16]([Cl:17])=[CH:15][CH:14]=[CH:13][N:12]=1.C([O-])([O-])=O.[K+].[K+].C(O)(C(F)(F)F)=O>CS(C)=O>[Cl:17][C:16]1[C:11]([N:1]2[CH2:2][CH:3]=[C:4]([C:7]([OH:9])=[O:8])[CH2:5][CH2:6]2)=[N:12][CH:13]=[CH:14][CH:15]=1Participants
6
Conditions
- Temperature
- 90 °C
Procedure
1,2,3,6-Tetrahydro-4-pyridinecarboxylic acid (7.0 g, 47 mmol) and 2-bromo-3-chloropyridine (11.0 g, 57 mmol) were combined in DMSO (100 mL) and treated with anhydrous K2CO3 (8.0 g, 58 mmol). The mixture was heated at 90° C. overnight, allowed to cool to room temperature, and then concentrated under reduced pressure. The residue in dichloromethane (200 mL) was cooled to −78° C. and treated with an excess of TFA (10 mL, 130 mmol) dropwise. The mixture was allowed to warm to room temperature and the layers were separated. The organic layer was washed with brine, dried over Na2SO4, filtered, and the filtrate concentrated under reduced pressure to provide the title compound which was used in the next step without further purification.
Workup
- temperatureto cool to room temperature
- concentrationconcentrated under reduced pressure
- temperatureThe residue in dichloromethane (200 mL) was cooled to −78° C.
- temperatureto warm to room temperature
- customthe layers were separated
- washThe organic layer was washed with brine
- dry with materialdried over Na2SO4
- filtrationfiltered
- concentrationthe filtrate concentrated under reduced pressure
Sources & evidence
- ORD record
- ord-99223bcc31de400fa2512248238e07c7
- Source dataset
- uspto-grants-2006_10
- Patent number
- US07129235B2
Reaction notes
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