Dichloromethane → 8-(trans-3-Fluoropiperidin-4-yloxy)quinoline dihydrochloride
Reaction equation
[F:1][C@H:2]1[C@H:7]([O:8][C:9]2[CH:10]=[CH:11][CH:12]=[C:13]3[C:18]=2[N:17]=[CH:16][CH:15]=[CH:14]3)[CH2:6][CH2:5][N:4](C(OC(C)(C)C)=O)[CH2:3]1.C(O)(C(F)(F)F)=O.C(Cl)[Cl:34]>>[ClH:34].[ClH:34].[F:1][C@H:2]1[C@H:7]([O:8][C:9]2[CH:10]=[CH:11][CH:12]=[C:13]3[C:18]=2[N:17]=[CH:16][CH:15]=[CH:14]3)[CH2:6][CH2:5][NH:4][CH2:3]1Participants
Procedure
To a solution of (trans)-tert-butyl 3-fluoro-4-(quinolin-8-yloxy)piperidine-1-carboxylate (5.4 g, 15.6 mmol) in 100 mL DCM was added neat TFA (24.0 ml, 311.78 mmol). The reaction mixture was stirred at ambient temperature for 4 hours, after which it was concentrated. The resulting residue was dissolved in 40 mL DCM, and this solution was added dropwise by addition funnel to a flask containing vigorously stirring 60 mL 2 M HCl in ether in 500 mL ether, causing precipitation. The solids were isolated by filtration through a medium pore glass fritted funnel by forcing solvent through the frit with nitrogen pressure, rinsed with ether, and dried in vacuo to give 8-(trans-3-fluoropiperidin-4-yloxy)quinoline dihydrochloride (6.6 g, 21 mmol) as a solid which was used without further purification in the next step. LC/MS ESI (+) m/z 247 (M+H)− detected.
Workup
- concentrationafter which it was concentrated
- dissolutionThe resulting residue was dissolved in 40 mL DCM
- additionthis solution was added dropwise by addition funnel to a flask
- additioncontaining vigorously
- stirringstirring 60 mL 2 M HCl in ether in 500 mL ether
- customprecipitation
- customThe solids were isolated by filtration through a medium pore glass fritted funnel
- washrinsed with ether
- customdried in vacuo
Sources & evidence
- ORD record
- ord-bb6318d296bd4fe6a004cb6b5595586c
- Source dataset
- uspto-grants-2012_03
- Patent number
- US08138181B2
Reaction notes
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