Hydrochloric Acid → 3-Benzyl-N-methoxy-N,2,4-trimethylquinoline-6-carboxamide

HRID 928766Notes

Reaction equation

HRID 928766 reaction equation
[CH2:1]([C:8]1[C:9]([CH3:24])=[N:10][C:11]2[C:16]([C:17]=1[CH3:18])=[CH:15][C:14]([C:19](OCC)=[O:20])=[CH:13][CH:12]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:25][NH:26][O:27][CH3:28].Cl.C([Mg]Cl)(C)C>C1COCC1>[CH2:1]([C:8]1[C:9]([CH3:24])=[N:10][C:11]2[C:16]([C:17]=1[CH3:18])=[CH:15][C:14]([C:19]([N:26]([O:27][CH3:28])[CH3:25])=[O:20])=[CH:13][CH:12]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14232N,O-DimethylhydroxylamineHCID 86715607Ethyl 3-benzyl-2,4-dimethylquinoline-6-carboxylate2×HCID 178418918HCID 178418918, compound

Product 1

HCID 867156093-Benzyl-N-methoxy-N,2,4-trimethylquinoline-6-carboxamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A slurry of ethyl 3-benzyl-2,4-dimethylquinoline-6-carboxylate (99.5 mg, 0.312 mmol, Intermediate 34: step b) and N,O-dimethylhydroxylamine.HCl (42.2 mg, 0.433 mmol) in THF (1 mL) was stirred at 0° C. under argon while iPrMgCl (2.01 M in THF, 0.43 mL, 0.864 mmol) was added dropwise. The resulting dark solution was stirred at 0° C. overnight while the ice bath expired. It was then quenched with 5 M aqueous NH4Cl (4 mL) and extracted with EtOAc (2×3 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated, and the residue was flash chromatographed with a heptane to 100% EtOAc gradient to yield the title compound as an amber oil.

Workup

  1. additionwas added dropwise
  2. customIt was then quenched with 5 M aqueous NH4Cl (4 mL)
  3. extractionextracted with EtOAc (2×3 mL)
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customchromatographed with a heptane to 100% EtOAc gradient

Sources & evidence

ORD record
ord-ff59fc8934594befa2d462f531d46883
Source dataset
uspto-grants-2016_03
Patent number
US09290476B2

Reaction notes

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