1,10-Phenanthroline → 2-((2-Chloropyridin-4-yloxy)methyl)-3,5-difluoropyridine

HRID 1918504Notes

Reaction equation

[F:1][C:2]1[C:3]([CH2:9][OH:10])=[N:4][CH:5]=[C:6]([F: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:11][C:12]1[CH:17]=[C:16]([O:10][CH2:9][C:3]2[C:2]([F:1])=[CH:7][C:6]([F:8])=[CH:5][N:4]=2)[CH:15]=[CH:14][N:13]=1

Participants

Conditions

Temperature: 105 °C

Procedure

(3,5-Difluoropyridin-2-yl)methanol (4.15 g, 28.4 mmol), 2-chloro-4-iodopyridine (7.47 g, 31.2 mmol), cesium carbonate (12.0 g, 36.3 mmol), CuI (5.40 g, 28.4 mmol) and 1,10-phenanthroline (1.02 g, 5.60 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 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 eluting with ethyl acetate/hexanes; gradient 100% hexanes to 60% ethyl acetate) to provide the title compound (3.42 g, 47%) as a yellow oil: ESI MS m/z 257 [M+H]+.

Workup

customdegassed with a nitrogen stream for 10 minutes
temperatureallowed cool
filtrationfiltered through a silica plug
washeluting with ethyl acetate
concentrationThe filtrate was concentrated
customthe residue was purified by column chromatography (80 g ISCO column eluting with ethyl acetate/hexanes; gradient 100% hexanes to 60% ethyl acetate)

Sources & evidence

ORD record: ord-2bd252c01bd24cbaafda9fcae7f29e5f
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08618299B2

Reaction notes

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