Morpholine → Methyl 6-morpholinonicotinate
Reaction equation
Cl[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][N:3]=1.[NH:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1>CO>[N:12]1([C:2]2[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][N:3]=2)[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
There was dissolved, in methanol (50 mL), methyl 6-chloro-nicotinate (4.00 g, 23.3 mM), then morpholine (6.10 mL, 69.9 mM) was added to the solution and the solution was stirred for 14 hours while refluxing the same with heating. The solvent was distilled off from this reaction liquid, the resulting residue was diluted with water and then extracted with ethyl acetate. The resulting extracts were combined, dried over anhydrous sodium sulfate, the solvent was distilled off to thus obtain methyl 6-(morpholin-4-yl)-nicotinate (4.07 g, yield: 79%). Subsequently, acetonitrile (1.61 mL, 30.6 mM) was added to a solution of 18-crown-6 (476 mg, 1.80 mM) and potassium tert-butoxide (1M THF solution, 27.0 mL, 27.0 mM) in THF (10 mL) at 60° C. and then the mixture was stirred for 5 minutes. To this solution, there was added the methyl 6-(morpholin-4-yl)-nicotinate (4.00 g, 18.0 mM) prepared above and the mixture was stirred for 30 minutes. This suspension was filtered and the resulting solid was washed with diethyl ether.
Workup
- temperaturewhile refluxing the same
- temperaturewith heating
- distillationThe solvent was distilled off from this reaction liquid
- additionthe resulting residue was diluted with water
- extractionextracted with ethyl acetate
- dry with materialdried over anhydrous sodium sulfate
Sources & evidence
- ORD record
- ord-915fe67197624ea2becb1eac46aed5c5
- Source dataset
- uspto-grants-2012_11
- Patent number
- US08314098B2
Reaction notes
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