4-Methylmorpholine → N,2-dimethoxy-N-methyl-2-(quinolin-5-yl)acetamide

HRID 56529Notes

Reaction equation

HRID 56529 reaction equation
[CH3:1][O:2][CH:3]([C:7]1[CH:16]=[CH:15][CH:14]=[C:13]2[C:8]=1[CH:9]=[CH:10][CH:11]=[N:12]2)[C:4]([OH:6])=O.CN1CCOCC1.ClC(OCC(C)C)=O.Cl.[CH3:33][NH:34][O:35][CH3:36]>C(Cl)Cl>[CH3:36][O:35][N:34]([CH3:33])[C:4](=[O:6])[CH:3]([O:2][CH3:1])[C:7]1[CH:16]=[CH:15][CH:14]=[C:13]2[C:8]=1[CH:9]=[CH:10][CH:11]=[N:12]2

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 584320332-Methoxy-2-(quinolin-5-yl)acetic acid

Product 1

HCID 58432006N,2-dimethoxy-N-methyl-2-(quinolin-5-yl)acetamideYield 60%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To an ice-cold solution of 2-methoxy-2-(quinolin-5-yl)acetic acid (2.8 g, 12.9 mmol) in anhydrous CH2Cl2 (50 mL) and NMM (3.1 mL, 29 mmol) under argon was added isobutyl chloroformate (1.9 mL, 14 mmol) dropwise. After stirring over an ice bath for 40 min, N,O-dimethylhydroxylamine hydrochloride (1.63 g, 16.8 mmol) was added in three aliquots over a period of 15 min. The mixture was stirred for 15 min then the ice bath was removed. After 24 hrs, saturated aqueous NaHCO3 was added and stirred for 30 min. The layers were separated and the aqueous layer was extracted with CH2Cl2. The combined organics were washed with saturated aqueous NaHCO3, H2O and brine, dried over Na2SO4 and concentrated in vacuo. Purification by chromatography (0-100% EtOAc-hexanes) gave N,2-dimethoxy-N-methyl-2-(quinolin-5-yl)acetamide as an oil which became crystalline upon standing (1.8 g, 60% yield).

Workup

  1. stirringThe mixture was stirred for 15 min
  2. customthe ice bath was removed
  3. waitAfter 24 hrs
  4. additionsaturated aqueous NaHCO3 was added
  5. stirringstirred for 30 min
  6. customThe layers were separated
  7. extractionthe aqueous layer was extracted with CH2Cl2
  8. washThe combined organics were washed with saturated aqueous NaHCO3, H2O and brine
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated in vacuo
  11. customPurification by chromatography (0-100% EtOAc-hexanes)

Sources & evidence

ORD record
ord-8b01411462c34a3a88e7578a6399c395
Source dataset
uspto-grants-2016_09
Patent number
US09434707B2

Reaction notes

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