1,10-Phenanthroline → 2-Chloro-4-((6-methylpyridin-3-yl)methoxy)pyridine

HRID 1918487Notes

Reaction equation

[CH3:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][OH:9])=[CH:4][CH:3]=1.[Cl:10][C:11]1[CH:16]=[C:15](I)[CH:14]=[CH:13][N:12]=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:10][C:11]1[CH:16]=[C:15]([O:9][CH2:8][C:5]2[CH:6]=[N:7][C:2]([CH3:1])=[CH:3][CH:4]=2)[CH:14]=[CH:13][N:12]=1

Participants

Conditions

Temperature: 105 °C

Procedure

(6-Methylpyridin-3-yl)methanol (3.25 g, 26.4 mmol), 2-chloro-4-iodopyridine (5.7 g, 24 mmol), cesium carbonate (10.1 g, 31.2 mmol), CuI (0.90 g, 4.8 mmol) and 1,10-phenanthroline (0.86 g, 4.8 mmol) were stirred in toluene (15 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 100% ethyl acetate) to provide the title compound (4.2 g, 75%) as a white solid: 1H NMR (300 MHz, CDCl3) δ 8.54 (d, J=2.0 Hz, 1H), 8.21 (d, J=5.7 Hz, 1H), 7.65-7.62 (dd, J=7.9, 2.2 Hz, 1H), 7.21 (d, J=7.9 Hz, 1H), 6.91 (d, J=2.2 Hz, 1H), 6.83-6.80 (dd, J=5.8, 2.2 Hz, 1H), 5.08 (s, 2H), 2.59 (s, 3H).

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 100% ethyl acetate)

Sources & evidence

ORD record: ord-01a54d7e143b44fcb44a325dff5c1f43
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08618299B2

Reaction notes

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