1,10-Phenanthroline → 3,5-Dichloro-2-((2-chloropyridin-4-yloxy)methyl)pyridine

HRID 474945Notes

Reaction equation

HRID 474945 reaction equation
[Cl:1][C:2]1[C:3]([CH2:9][OH:10])=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1.[Cl:11][C:12]1[CH:17]=[C:16](I)[CH:15]=[CH:14][N:13]=1.C(=O)([O-])[O-].[Cs+].[Cs+].N1C2C(=CC=C3C=2N=CC=C3)C=CC=1>C1(C)C=CC=CC=1.[Cu]I>[Cl:1][C:2]1[C:3]([CH2:9][O:10][C:16]2[CH:15]=[CH:14][N:13]=[C:12]([Cl:11])[CH:17]=2)=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

7

Reactant 4

HCID 13181,10-PhenanthrolineHCID 10796Cesium carbonateHCID 15165112-Chloro-4-iodopyridineHCID 17750383(3,5-Dichloro-pyridin-2-yl)-methanol

Product 1

HCID 580934283,5-Dichloro-2-((2-chloropyridin-4-yloxy)methyl)pyridineYield 38.2%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
105 °C

Procedure

(3,5-Dichloropyridin-2-yl)methanol (2.00 g, 10.4 mmol), 2-chloro-4-iodopyridine (2.49 g, 10.4 mmol), cesium carbonate (4.41 g, 13.5 mmol), CuI (1.97 g, 10.4 mmol) and 1,10-phenanthroline (374 mg, 2.08 mmol) were stirred in toluene (20 mL) and degassed with a nitrogen stream for 10 minutes. The mixture was heated to 105° C. for 16 h, allowed to cool and filtered through a silica plug eluting with ethyl acetate. The filtrate was concentrated, and the resulting residue was purified by column chromatography (80 g ISCO column column eluting with ethyl acetate/hexanes; gradient 100% hexanes to 40% ethyl acetate) to provide the title compound (1.15 g, 38%) as an orange solid: 1H NMR (300 MHz, CDCl3) δ 8.50 (d, J=2.1 Hz, 1H), 8.21 (d, J=5.8 Hz, 1H), 7.80 (d, J=2.1 Hz, 1H), 6.97 (d, J=2.2 Hz, 1H), 6.88-6.85 (dd, J=5.8, 2.2 Hz, 1H), 5.31 (s, 2H).

Workup

  1. customdegassed with a nitrogen stream for 10 minutes
  2. temperatureto cool
  3. filtrationfiltered through a silica plug
  4. washeluting with ethyl acetate
  5. concentrationThe filtrate was concentrated
  6. customthe resulting residue was purified by column chromatography (80 g ISCO column column eluting with ethyl acetate/hexanes; gradient 100% hexanes to 40% ethyl acetate)

Sources & evidence

ORD record
ord-8fbb1590d17043ef929a3709b78a9428
Source dataset
uspto-grants-2014_01
Patent number
US08637501B2

Reaction notes

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