Water → HCID 178426682, compound
Reaction equation
Cl[C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][N+:3]=1[O-:9].[NH2:10][C@@H:11]1[CH2:16][CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12]1.C(N(C(C)C)CC)(C)C.O>CCCCO.CN(C1C=CN=CC=1)C>[C:20]([O:19][C:17]([N:13]1[CH2:14][CH2:15][CH2:16][C@@H:11]([NH:10][C:2]2[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][N+:3]=2[O-:9])[CH2:12]1)=[O:18])([CH3:23])([CH3:21])[CH3:22]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 100 °C
Procedure
To a solution of the compound from Step 1 2-chloro-3-methylpyridine 1-oxide (14.5 g, 101 mmol) and tert-butyl (3R)-3-aminopiperidine-1-carboxylate (24.27 g, 121.2 mmol) in n-BuOH (120 mL) were added diisopropylethyl amine (14.35 g, 111 mmol) and DMAP (1.22 g, 9.99 mmol) slowly at 0° C. The resulting mixture was heated at 100° C. for 36 h. The reaction was cooled, and water was added. The mixture was then extracted with EtOAc (3×50 mL). The combined organic layers were dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The crude compound was purified by silica gel chromatography eluting with a gradient of petroleum ether:EtOAc (80:20 to 50:50) to afford the title compound (7.9 g, 25%) as a yellow oil.
Workup
- temperatureThe reaction was cooled
- extractionThe mixture was then extracted with EtOAc (3×50 mL)
- dry with materialThe combined organic layers were dried over Na2SO4
- filtrationfiltered
- concentrationthe filtrate was concentrated under reduced pressure
- customThe crude compound was purified by silica gel chromatography
- washeluting with a gradient of petroleum ether:EtOAc (80:20 to 50:50)
Sources & evidence
- ORD record
- ord-5b9de9eff72e4b36bbf23246727d2bd2
- Source dataset
- uspto-grants-2016_01
- Patent number
- US09227956B2
Reaction notes
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