4-Methylmorpholine → N,2-dimethoxy-N-methyl-2-(4-morpholinophenyl)acetamide
Reaction equation
[CH3:1][O:2][CH:3]([C:7]1[CH:12]=[CH:11][C:10]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[CH:9][CH:8]=1)[C:4]([OH:6])=O.CN1CCOCC1.C(OC(Cl)=O)C(C)C.Cl.[CH3:35][NH:36][O:37][CH3:38].C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH3:38][O:37][N:36]([CH3:35])[C:4](=[O:6])[CH:3]([O:2][CH3:1])[C:7]1[CH:12]=[CH:11][C:10]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[CH:9][CH:8]=1Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 1
Procedure
To a suspension of 2-methoxy-2-(4-morpholinophenyl)acetic acid (2.97 g, 11.8 mmol) in anhydr. CH2Cl2 (66 mL) in an oven-dried flask under argon was added N-methylmorpholine (3 mL, 27.3 mmol) and the resulting solution was cooled over ice. Isobutylchloroformate (1.8 mL, 13.76 mmol) was added dropwise. After stirring for 50 min, N,O-dimethylhydroxylamine hydrochloride (1.5 g, 15.3 mmol) was added and the mixture was allowed to warm slowly to room temp. After stirring for 16 hours, saturated aqueous NaHCO3 was added and the mixture stirred for >15 min. The mixture was diluted with CH2Cl2 and the layers were separated. The organics were washed with brine, dried over MgSO4/Na2SO4 and concentrated. Purification by chromatography (60-85% EtOAc-hexanes) gave N,2-dimethoxy-N-methyl-2-(4-morpholinophenyl) acetamide as an off-white solid (3.15 g, 90% yield).
Workup
- temperaturethe resulting solution was cooled over ice
- stirringAfter stirring for 16 hours
- stirringthe mixture stirred for >15 min
- customthe layers were separated
- washThe organics were washed with brine
- dry with materialdried over MgSO4/Na2SO4
- concentrationconcentrated
- customPurification by chromatography (60-85% EtOAc-hexanes)
Sources & evidence
- ORD record
- ord-b69588a655dd4d3e854e2f3481f10b76
- Source dataset
- uspto-grants-2016_09
- Patent number
- US09434707B2
Reaction notes
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