N,N'-Dimethylethylenediamine → tert-butyl N-[(3S)-1-(6-chloro-3-methyl-2-pyridyl)-6-oxo-3-piperidyl]carbamate

HRID 57923Notes

Reaction equation

HRID 57923 reaction equation
Br[C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[C:4]([Cl:9])[N:3]=1.[O:10]=[C:11]1[NH:16][CH2:15][C@@H:14]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH2:13][CH2:12]1.C(=O)([O-])[O-].[K+].[K+].CNCCNC>O1CCOCC1.[Cu]I>[Cl:9][C:4]1[N:3]=[C:2]([N:16]2[C:11](=[O:10])[CH2:12][CH2:13][C@H:14]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:22])([CH3:21])[CH3:23])[CH2:15]2)[C:7]([CH3:8])=[CH:6][CH:5]=1

Participants

7

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 11430Potassium CarbonateHCID 15466433(S)-tert-butyl 6-oxopiperidin-3-ylcarbamateHCID 534166752-Bromo-6-chloro-3-methylpyridine

Product 1

HCID 86707113tert-butyl N-[(3S)-1-(6-chloro-3-methyl-2-pyridyl)-6-oxo-3-piperidyl]carbamateYield 55.1%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A solution containing 2-bromo-6-chloro-3-methylpyridine (487 mg, 2.24 mmol), tert-butyl N-[(3S)-6-oxo-3-piperidyl]carbamate (400 mg, 1.87 mmol), Copper(I) iodide (356 mg, 1.87 mmol), Potassium carbonate (310 mg, 2.24 mmol) and N,N′-Dimethylethylenediamine (329 mg, 3.73 mmol) in dioxane 12 mL was stirred at 110° C. 18 h. The reaction was filtered through celite and concentrated. The crude product was purified by flash chromatography (EtOAc/Heptane eluted at 50% EtOAc) to give the desired product 350 mg 38% yield. MS (ESI) m/z: 340.1.

Workup

  1. custom18 h
  2. filtrationThe reaction was filtered through celite
  3. concentrationconcentrated
  4. customThe crude product was purified by flash chromatography (EtOAc/Heptane eluted at 50% EtOAc)

Sources & evidence

ORD record
ord-56fcae3fe5fa4a4ab12aa5d86af2828e
Source dataset
uspto-grants-2016_09
Patent number
US09434725B2

Reaction notes

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