Cesium carbonate → 2-Methoxy-4-((6-(trifluoromethyl)pyridin-3-yl)methoxy)pyridine

HRID 930710

Reaction equation

HRID 930710 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([O:8][CH3:9])[C:3]=1Br.[F:11][C:12]([F:22])([F:21])[C:13]1[N:18]=[CH:17][C:16]([CH2:19][OH:20])=[CH:15][CH:14]=1.CC1C=NC2C(C=1C)=CC=C1C=2N=CC(C)=C1C.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.[Cu]I>[CH3:9][O:8][C:4]1[CH:3]=[C:2]([O:20][CH2:19][C:16]2[CH:17]=[N:18][C:13]([C:12]([F:22])([F:11])[F:21])=[CH:14][CH:15]=2)[CH:7]=[CH:6][N:5]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 742653,4,7,8-Tetramethyl-1,10-phenanthrolineHCID 36138956-(Trifluoromethyl)pyridine-3-methanolHCID 134797633,4-Dibromo-2-methoxypyridine

Product 1

HCID 575147592-Methoxy-4-((6-(trifluoromethyl)pyridin-3-yl)methoxy)pyridineYield 72.4%

Reagents, catalysts & solvents 2

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

Procedure

4-BromoBromo-2-methoxypyridine (3.06 g, 16.2 mmol), (6-(trifluoromethyl)pyridin-3-yl)methanol (2.74 g, 15.5 mmol), 3,4,7,8-tetramethylphenanthroline (0.36 g, 0.15 mmol), CuI (0.14 g, 0.74 mmol) and Cs2CO3 (7.57 g, 23.2 mmol) were combined in toluene (15 mL) and heated to reflux under a nitrogen atmosphere for 16 h. Upon cooling the mixture was purified by flash column chromography (silica gel, hexanes/EtOAc, 1:0 to 1:1) to provide the title compound (3.19 g, 72%) as a red oil: 1H NMR (300 MHz, CDCl3) δ 8.78 (s, 1H), 8.02 (d, J=5.9 Hz, 1H), 7.95 (d, J=8.1 Hz, 1H), 7.32 (d, J=8.0 Hz, 1H), 6.55 (dd, J=5.9, 2.2 Hz, 1H), 6.26 (d, J=2.2 Hz, 1H), 5.16 (s, 2H), 3.93 (s, 3H).

Workup

  1. temperatureheated
  2. temperatureto reflux under a nitrogen atmosphere for 16 h
  3. temperatureUpon cooling the mixture
  4. customwas purified by flash column chromography (silica gel, hexanes/EtOAc, 1:0 to 1:1)

Sources & evidence

ORD record
ord-2a6b966a1eba4995b56a76c5b469d498
Source dataset
uspto-grants-2016_03
Patent number
US09296743B2

Linked notes

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