Methanol → 6-(chloromethyl)-N,N-dimethylpicolinamide

HRID 912527Notes

Reaction equation

HRID 912527 reaction equation
S([Cl:5])(C)(=O)=O.O[CH2:7][C:8]1[N:13]=[C:12]([C:14]([N:16]([CH3:18])[CH3:17])=[O:15])[CH:11]=[CH:10][CH:9]=1.CCN(C(C)C)C(C)C.CO>C(Cl)Cl.CCOC(C)=O>[Cl:5][CH2:7][C:8]1[N:13]=[C:12]([C:14]([N:16]([CH3:18])[CH3:17])=[O:15])[CH:11]=[CH:10][CH:9]=1

Participants

7

Reactant 4

HCID 887Methanol2×HCID 31297Methanesulfonyl chloride2×HCID 81531DiisopropylethylamineHCID 594106466-(hydroxymethyl)-N,N-dimethylpicolinamide

Product 1

HCID 671448016-(chloromethyl)-N,N-dimethylpicolinamide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Mesyl chloride (0.924 mmol, 71.5 μl, 106 mg) was added to a stirred solution of 6-(hydroxymethyl)-N,N-dimethylpicolinamide (0.616 mmol, 111 mg) and DIPEA (1.232 mmol, 204 μl, 159 mg) in DCM (2000 μl) at 0° C. The reaction was allowed to warm to room temperature and stirred for two hours. The mixture was diluted with EtOAc (20 mL) and an excess of MeOH added. Stirring was continued for 15 minutes then the mixture washed with water. Organics were dried over sodium sulphate and solvent evaporated. NMR showed desired product obtained but MsCl remaining. The residue was re-dissolved in DCM and MeOH and heated to 40° C. for 15 minutes. Solvent was evaporated under reduced pressure to yield 6-(chloromethyl)-N,N-dimethylpicolinamide. 1H NMR (CDCl3) δ: 7.88 (t, 1H), 7.62 (d, 1H), 7.52 (d, 1H), 5.34 (s, 2H), 3.15 (s, 6H).

Workup

  1. stirringStirring
  2. waitwas continued for 15 minutes
  3. washthe mixture washed with water
  4. dry with materialOrganics were dried over sodium sulphate and solvent
  5. customevaporated
  6. customobtained
  7. customSolvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-a0e0f515139a4417b7deebad92ed9fab
Source dataset
uspto-grants-2011_09
Patent number
US08026236B2

Reaction notes

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