Morpholine → 4-(5-bromopyridin-2-yl)morpholine

HRID 1454411Notes

Reaction equation

HRID 1454411 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=1.[NH:9]1[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1.C(=O)([O-])[O-].[Cs+].[Cs+]>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].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Br:8][C:5]1[CH:6]=[CH:7][C:2]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)=[N:3][CH:4]=1

Participants

7

Reactant 3

HCID 8083MorpholineHCID 10796Cesium carbonateHCID 693532,5-Dibromopyridine

Product 1

HCID 109667244-(5-bromopyridin-2-yl)morpholineYield 60%

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

2,5-Dibromopyridine (7.1 g, 30 mmol), morpholine (1.74 mL, 20 mmol), cesium carbonate (9.1 g, 28 mmol), tris(dibenzylideneacetone)dipalladium(0) (183 mg, 0.2 mmol), and racemic 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (374 mg, 0.6 mmol) in toluene (20 mL) was heated at 120° C. for 24 hours. After cooling to room temperature, the mixture was filtered through Celite™ and the Celite™ pad was washed with chloroform. The solution was concentrated in vacuo and was purified by silica gel chromatography (200:1 chloroform-methanol) to give 2.9 g (60% yield) of the title compound. 13C NMR (100 MHz, CDCl3) d 158.3, 148.7, 140.0, 108.4, 66.8, 45.7; MS (AP/Cl) 243.0, 245.0 (M+H)+.

Workup

  1. filtrationthe mixture was filtered through Celite™
  2. washthe Celite™ pad was washed with chloroform
  3. concentrationThe solution was concentrated in vacuo
  4. customwas purified by silica gel chromatography (200:1 chloroform-methanol)

Sources & evidence

ORD record
ord-788bed60232949dda7f438e15b6145a1
Source dataset
uspto-grants-2009_01
Patent number
US07479559B2

Reaction notes

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