4-Chloro-2-methylpyridine hydrochloride → HCID 66805338, compound

HRID 1193350Notes

Reaction equation

HRID 1193350 reaction equation
[C:1]([N:8]([CH3:13])[CH:9]1[CH2:12][NH:11][CH2:10]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].Cl.Cl[C:16]1[CH:21]=[CH:20][N:19]=[C:18]([CH3:22])[CH:17]=1>CC(O)C.C(OCC)(=O)C.C(=O)([O-])O.[Na+]>[CH3:13][N:8]([CH:9]1[CH2:12][N:11]([C:16]2[CH:21]=[CH:20][N:19]=[C:18]([CH3:22])[CH:17]=2)[CH2:10]1)[C:1](=[O:2])[O:3][C:4]([CH3:7])([CH3:6])[CH3:5]

Participants

6

Reactant 2

HCID 27628414-Chloro-2-methylpyridine hydrochlorideHCID 23033645tert-Butyl azetidin-3-yl(methyl)carbamate

Product 1

HCID 66805338HCID 66805338, compoundYield 51%

Reagents, catalysts & solvents 3

HCID 3776IsopropanolSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

3-(Boc-methylamino)azetidine (2.74 mmol, 1.0 eq) and 4-chloro-2-methylpyridine HCl (8.21 mmol, 3.0 eq) were dissolved in 2-propanol (5 ml) and DI PEA (13.69 mmol. 5.0 eq) and refluxed for 24 hours. After monitoring by TLC, the reaction solution was diluted with ethyl acetate and sat. sodium hydrogen carbonate solution, and the phases were separated. The aqueous phase was washed with ethyl acetate. The combined organic phases were washed 1× with sat. NaCl solution, dried over magnesium sulfate, concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel, ethyl acetate:ethanol 10:1+ammonia solution). Yield: 51%

Workup

  1. temperatureDI PEA (13.69 mmol. 5.0 eq) and refluxed for 24 hours
  2. customthe phases were separated
  3. washThe aqueous phase was washed with ethyl acetate
  4. washThe combined organic phases were washed 1× with sat. NaCl solution
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by column chromatography (silica gel, ethyl acetate:ethanol 10:1+ammonia solution)

Sources & evidence

ORD record
ord-749c85f60e9e44dca116dd0ffefe3af8
Source dataset
uspto-grants-2014_03
Patent number
US08680159B2

Reaction notes

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