4-Methylmorpholine → 2-Chloro-N-methoxy-N-methylisonicotinamide

HRID 1095872Notes

Reaction equation

HRID 1095872 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][N:10]=1)[C:5](O)=[O:6].Cl.[CH3:12][NH:13][O:14][CH3:15].CN1CCOCC1.CCN=C=NCCCN(C)C.Cl>CN(C1C=CN=CC=1)C.ClCCl.O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][N:10]=1)[C:5]([N:13]([O:14][CH3:15])[CH3:12])=[O:6]

Participants

8

Reactant 4

HCID 79724-MethylmorpholineHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 2369852-Chloroisonicotinic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 185068942-Chloro-N-methoxy-N-methylisonicotinamideYield 97.7%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of 2-chloroisonicotinic acid (20 g, 0.127 mol), N,O-dimethyl-hydroxylamine HCl (19.8 g, 0.203 mol), 4-methylmorpholine (20.5 g, 0.203 mol) and DMAP (1.55 g, 0.013 mol) in dichloromethane (300 ml) at 0° C. was added EDCI HCl (29.2 g, 0.152 mol). The mixture was stirred at 0° C. for 10 min and at room temperature for 17 h. The mixture was poured into water/1M aqueous HCl and extracted with dichloromethane. The combined organic phases were washed with water, saturated aqueous NaHCO3 solution and brine. The organic layer was dried over MgSO4, filtered and concentrated to give the title compound (24.9 g) as a white solid. MS(m/e)=201.2 [M+H+].

Workup

  1. extractionextracted with dichloromethane
  2. washThe combined organic phases were washed with water, saturated aqueous NaHCO3 solution and brine
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-3512f20f28114edd83377bf829793810
Source dataset
uspto-grants-2012_03
Patent number
US08138189B2

Reaction notes

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