Oxalyl chloride → N-Methoxy-N-methylquinoline-6-carboxamide

HRID 2176616Notes

Reaction equation

HRID 2176616 reaction equation
[N:1]1[C:10]2[C:5](=[CH:6][C:7]([C:11]([OH:13])=O)=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.C(Cl)(=O)C(Cl)=O.CCN(C(C)C)C(C)C.Cl.[CH3:30][O:31][NH:32][CH3:33]>CN(C=O)C.C(Cl)Cl>[CH3:30][O:31][N:32]([CH3:33])[C:11]([C:7]1[CH:6]=[C:5]2[C:10](=[CH:9][CH:8]=1)[N:1]=[CH:2][CH:3]=[CH:4]2)=[O:13]

Participants

7

Reactant 4

HCID 65578Oxalyl chlorideHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 825716-Quinolinecarboxylic acid

Product 1

HCID 55211172N-Methoxy-N-methylquinoline-6-carboxamideYield 95.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent3×

Procedure

A 250 mL RB flask was charged with quinoline-6-carboxylic acid (5.00 g, 28.9 mmol), DCM (100 ml, 1554 mmol), oxalyl chloride (3.79 ml, 43.3 mmol), and a few drops of DMF and stirred at RT for 2 hours, then concentrated. The residue was taken up in DCM (100 ml, 1554 mmol), cooled to 0° C., then Hunig's Base (17.7 ml, 101 mmol) and N-methoxymethanamine hydrochloride (2.96 g, 30.3 mmol) were added slowly. The mixture was stirred at room temperature for 16 hours (91463-3-1). The mixture was diluted with DCM (200 mL), then washed with water (250 mL), sat. NaHCO3 (250 mL), and brine (250 mL). The organic layer was dried with MgSO4, filtered, and concentrated to give a brown oil, which was purified by MPLC eluting with 2-6% MeOH/DCM to give N-methoxy-N-methylquinoline-6-carboxamide (5.943 g, 95.2% yield) as a brown oil.

Workup

  1. concentrationconcentrated
  2. temperaturecooled to 0° C.
  3. washwashed with water (250 mL), sat. NaHCO3 (250 mL), and brine (250 mL)
  4. dry with materialThe organic layer was dried with MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a brown oil, which
  8. customwas purified by MPLC
  9. washeluting with 2-6% MeOH/DCM

Sources & evidence

ORD record
ord-8a9f05aecab648e38f8060aefe13779c
Source dataset
uspto-grants-2015_06
Patent number
US09066954B2

Reaction notes

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