Morpholine → 4-(2-Fluoropyridin-3-yl)morpholine

HRID 1880050Notes

Reaction equation

HRID 1880050 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+]>C1(C)C=CC=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.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]=1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 70095012-Fluoro-3-iodopyridineHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 23676156Sodium t-butoxide

Product 1

HCID 585476984-(2-Fluoropyridin-3-yl)morpholine

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
150 °C

Procedure

A microwave reaction vessel was charged with 2-fluoro-3-iodopyridine (1.0211 g, 4.579 mmol), morpholine (0.3989 mL, 4.579 mmol), Pd2(dba)3 (0.2633 g, 0.2748 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (0.2232 g, 0.5495 mmol), and sodium t-butoxide (1.1363 g, 13.74 mmol) in toluene (15 mL). 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). The solvent was evaporated. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Biotage™ pre-packed silica gel column (40M), eluting with a gradient of 1% to 5% methanol in DCM, to provide 4-(2-fluoropyridin-3-yl)morpholine.

Workup

  1. customA microwave reaction vessel
  2. customThe solvent was evaporated
  3. customchromatographed through a Biotage™ pre-packed silica gel column (40M)
  4. washeluting with a gradient of 1% to 5% methanol in DCM

Sources & evidence

ORD record
ord-87093cb456f747a8a5e58ff7d6f198e1
Source dataset
uspto-grants-2012_11
Patent number
US08318718B2

Reaction notes

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