Morpholine → 2-Morpholinomethyl-4-chloropyridine

HRID 2056952Notes

Reaction equation

HRID 2056952 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][N:3]=1.C1C(=O)N(Br)C(=O)C1.[NH:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1.C([O-])([O-])=O.[K+].[K+]>C(Cl)(Cl)(Cl)Cl.CN(C=O)C.CCOC(C)=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>[O:20]1[CH2:21][CH2:22][N:17]([CH2:1][C:2]2[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][N:3]=2)[CH2:18][CH2:19]1

Participants

9

Reactant 4

HCID 8083MorpholineHCID 11430Potassium CarbonateHCID 67184N-bromobutanimideHCID 5813924-Chloro-2-methylpyridine

Product 1

HCID 220252682-Morpholinomethyl-4-chloropyridine

Reagents, catalysts & solvents 4

HCID 7187Benzoyl PeroxideCatalystHCID 5943Carbon TetrachlorideSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of the 2-methyl-4-chloropyridine (1.00 g, 7.84 mmol), NBS (1.42 g, 8.00 mmol) and benzoyl peroxide (˜10 mg) in 10 mL of CCl4 was heated at reflux for 5 h. After cooling down, the reaction mixture was filtered and filtrate was concentrated to give the crude products mixture, which was dissolved in DMF and treated with morpholine (1.00 mL) and K2CO3 (1 g). The mixture was stirred overnight. The mixture was then diluted with EtOAc, washed with water, brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by column chromatography on SiO2 to give 400 mg of the desired 2-morpholinomethyl-4-chloropyridine.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 5 h
  3. temperatureAfter cooling down
  4. filtrationthe reaction mixture was filtered
  5. concentrationfiltrate was concentrated
  6. customto give the crude products mixture, which
  7. washwashed with water, brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude product was purified by column chromatography on SiO2

Sources & evidence

ORD record
ord-68121c0892204dfb9706e1ed8059c0bf
Source dataset
uspto-grants-2008_02
Patent number
US07335657B2

Reaction notes

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