Morpholine → 4-(2-Fluoropyridin-3-yl)morpholine
Reaction equation
[F:1][C:2]1[C:7](I)=[CH:6][CH:5]=[CH:4][N:3]=1.[NH:9]1[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.CC(C)([O-])C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:1][C:2]1[C:7]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)=[CH:6][CH:5]=[CH:4][N:3]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 150 °C
Procedure
A microwave reaction vessel was charged with 2-fluoro-3-iodopyridine (purchased from Maybridge™) (0.565 g, 2.53 mmol), morpholine (purchased from Aldrich™) (0.221 ml, 2.53 mmol), Pd2(dba)3 (purchased from Strem™) (0.154 g, 0.152 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (purchased from Strem™) (0.135 g, 0.304 mmol), and sodium t-butoxide (0.8 g, 7.6 mmol). The reaction mixture was stirred and heated in a Discover® model microwave reactor (CEM, Matthews, N.C.) at 150° C. for 20 min (125 watts, Powermax feature on, ramp time 5 min). Solvent was evaporated. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Biotage pre-packed silica gel column, eluting with a gradient of 1% to 5% MeOH in CH2Cl2, to provide 4-(2-fluoropyridin-3-yl)morpholine (0.311 g, 67.5% yield).
Workup
- customA microwave reaction vessel
- customSolvent was evaporated
- customchromatographed through a Biotage pre-packed silica gel column
- washeluting with a gradient of 1% to 5% MeOH in CH2Cl2
Sources & evidence
- ORD record
- ord-4095339666d34f4d83fd25904c2c9376
- Source dataset
- uspto-grants-2016_06
- Patent number
- US09376450B2
Reaction notes
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