tert-butyl 4-(2-chloro-3-fluorophenyl)-5,6-dihydropyridine-1(2H)-carboxylate → Tert-butyl-4-(2-chloro-3-fluorophenyl)piperidine-1 carboxylate
Reaction equation
[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C:9]1[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH:10]=1>CCOC(C)=O.O=[Pt]=O>[C:18]([O:17][C:15]([N:12]1[CH2:11][CH2:10][CH:9]([C:3]2[CH:4]=[CH:5][CH:6]=[C:7]([F:8])[C:2]=2[Cl:1])[CH2:14][CH2:13]1)=[O:16])([CH3:21])([CH3:19])[CH3:20]Participants
Procedure
A mixture of tert-butyl 4-(2-chloro-3-fluorophenyl)-5,6-dihydropyridine-1(2H)-carboxylate (12, 0.488 g, 1.41 mmol) and PtO2 (0.109 g, 0.48 mmol) in EtOAc (15 mL) was stirred at ambient temperature for 18 h under a balloon of H2. The mixture was filtered over Celite, and the filtrate was concentrated under reduced pressure and dissolved in CH2Cl2 (4 mL). To this solution was added HCl (2 N in Et2O, 4.0 mL) and the resulting mixture stirred at ambient temperature for 20 min. The resulting suspension was diluted with Et2O (20 mL) and the solids were collected by filtration to provide tert-butyl-4-(2-chloro-3-fluorophenyl)piperidine-1 carboxylate (13) as a clear semi-solid (0.471 g, 95%): 1H NMR (300 MHz, DMSO-d6) δ 7.43-7.19 (m, 3H), 4.17-4.01 (m, 2H), 3.20-3.03 (m, 1H), 2.95-2.68 (m, 2H), 1.79-1.65 (m, 2H), 1.58-1.45 (m, 2H), 1.41 (s, 9H).
Workup
- filtrationThe mixture was filtered over Celite
- concentrationthe filtrate was concentrated under reduced pressure
- dissolutiondissolved in CH2Cl2 (4 mL)
- additionTo this solution was added HCl (2 N in Et2O, 4.0 mL)
- stirringthe resulting mixture stirred at ambient temperature for 20 min
- additionThe resulting suspension was diluted with Et2O (20 mL)
- filtrationthe solids were collected by filtration
Sources & evidence
- ORD record
- ord-915bfaaa158d494aaea1861137c5599a
- Source dataset
- uspto-grants-2016_09
- Patent number
- US09434727B2
Reaction notes
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