Water → tert-butyl (3R)-3-[(3-methylpyridin-2-yl)amino]piperidine-1-carboxylate
Reaction equation
Br[C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][N:3]=1.[NH2:9][C@@H:10]1[CH2:15][CH2:14][CH2:13][N:12]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:11]1.C([O-])([O-])=O.[Cs+].[Cs+].O>C1(C)C=CC=CC=1.C12(PC34CC(CC3)CC4)CC(CC1)CC2.CN(CC1[C-]([Pd]Cl)C=CC=1)C.[CH-]1C=CC=C1.[Fe+2].CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:8][C:7]1[C:2]([NH:9][C@@H:10]2[CH2:15][CH2:14][CH2:13][N:12]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:11]2)=[N:3][CH:4]=[CH:5][CH:6]=1Participants
8
Reactant 4
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 110 °C
Procedure
To a solution of 2-bromo-3-methylpyridine (75.0 g, 436 mmol) and tert-butyl (3R)-3-aminopiperidine-1-carboxylate (87.3 g, 436 mmol) in toluene (1.2 L) were added Cs2CO3 (426 g, 1.31 mol), 2-(dimethylaminomethyl)ferrocen-1-yl-palladium(II) chloride dinorbornylphosphine (MFCD05861622) (1.56 g, 4.36 mmol) and Pd(OAc)2 (0.490 g, 2.18 mmol) under N2 atmosphere. The mixture was stirred at 110° C. for 48 h. The mixture was cooled to room temperature then poured into water (500 mL) and extracted with EtOAc (3×300 mL). The organic layers were dried over Na2SO4, filtered, and the filtrate was concentrated in vacuo. The residue was purified by silica gel column chromatography to give the title compound as a yellow solid (65 g, 60%).
Workup
- temperatureThe mixture was cooled to room temperature
- extractionextracted with EtOAc (3×300 mL)
- dry with materialThe organic layers were dried over Na2SO4
- filtrationfiltered
- concentrationthe filtrate was concentrated in vacuo
- customThe residue was purified by silica gel column chromatography
Sources & evidence
- ORD record
- ord-8490e98b8ab94dc3b5cb98d81d58f731
- Source dataset
- uspto-grants-2016_01
- Patent number
- US09227956B2
Reaction notes
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