1,10-Phenanthroline → 2-Chloro-4-(pyridin-2-ylmethoxy)pyridine

HRID 469687Notes

Reaction equation

HRID 469687 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][OH:8].[Cl:9][C:10]1[CH:15]=[C:14](I)[CH:13]=[CH:12][N:11]=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:9][C:10]1[CH:15]=[C:14]([O:8][CH2:7][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)[CH:13]=[CH:12][N:11]=1

Participants

7

Reactant 4

HCID 13181,10-PhenanthrolineHCID 10796Cesium carbonateHCID 11474PiconolHCID 15165112-Chloro-4-iodopyridine

Product 1

HCID 580922552-Chloro-4-(pyridin-2-ylmethoxy)pyridineYield 74.3%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
105 °C

Procedure

Pyridin-2-ylmethanol (3.00 g, 27.5 mmol), 2-chloro-4-iodopyridine (6.0 g, 25 mmol), cesium carbonate (10.6 g, 32.5 mmol), CuI (0.95 g, 5.0 mmol) and 1,10-phenanthroline (0.90 g, 5.0 mmol) were stirred in toluene (15 mL) and purged with a nitrogen stream for 10 minutes. The mixture was heated to 105° C. for 16 h, allowed cool and filtered through a silica plug eluting with ethyl acetate. The filtrate was concentrated, and the residue was purified by column chromatography (80 g ISCO column column eluting with ethyl acetate/hexanes; gradient 100% hexanes to 100% ethyl acetate) to provide the title compound (4.1 g, 74%) as a white solid: ESI MS m/z 221 [M+H]+.

Workup

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

Sources & evidence

ORD record
ord-eaed99e176164be79163e83e70460a7a
Source dataset
uspto-grants-2014_01
Patent number
US08629158B2

Reaction notes

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