Cesium fluoride → 4-Chloro-6-(4-isopropoxyphenyl)-6'-methoxy-2,2'-bipyridine

HRID 523149

Reaction equation

HRID 523149 reaction equation
Cl[C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([O:15][CH:16]([CH3:18])[CH3:17])=[CH:11][CH:10]=2)[N:3]=1.[CH3:19][O:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([Sn](CCCC)(CCCC)CCCC)[N:22]=1.[F-].[Cs+]>[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:8][C:6]1[CH:5]=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([O:15][CH:16]([CH3:18])[CH3:17])=[CH:11][CH:10]=2)[N:3]=[C:2]([C:23]2[CH:24]=[CH:25][CH:26]=[C:21]([O:20][CH3:19])[N:22]=2)[CH:7]=1

Participants

6

Reactant 3

HCID 25953Cesium fluorideHCID 105248912-Methoxy-6-(tributylstannyl)pyridineHCID 901180792,4-Dichloro-6-(4-isopropoxyphenyl)pyridine

Product 1

HCID 901180714-Chloro-6-(4-isopropoxyphenyl)-6'-methoxy-2,2'-bipyridineYield 92%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Procedure

To a 2 dram vial equipped with a stir bar was added 2,4-dichloro-6-(4-isopropoxyphenyl)pyridine (50 mg, 0.18 mmol), 2-methoxy-6-(tributylstannyl)pyridine (701 mg, 0.178 mmol), CuI (9 mg, 0.05 mmol), CsF (82 mg, 0.54 mmol), and Pd(PPh3)4 (10 mg, 8.9 μmol). The vial was sealed with a septum screw-cap and then placed under N2 atmosphere. To the vial was added degassed DMF (1 mL). The vial was placed in a 80° C. heating block with stirring for 1 hour. The reaction mixture was allowed to cool to room temperature and was then directly purified via C18 chromatography (water:MeOH w/0.1% TFA) to afford 4-chloro-6-(4-isopropoxyphenyl)-6′-methoxy-2,2′-bipyridine as a dark solid (58 mg, 92%). 1H-NMR (500 MHz, CDCl3) 8.29 (d, J=1.7 Hz, 1H), 8.21 (dd, J=7.4, 0.5 Hz, 1H), 8.09-8.04 (m, 2H), 7.74 (t, J=7.8 Hz, 1H), 7.67 (d, J=1.7 Hz, 1H), 7.03-6.99 (m, 2H), 6.82 (dd, J=8.2, 0.5 Hz, 1H), 4.66 (spt, J=6.1 Hz, 1H), 4.08 (s, 3H), 1.40 (d, J=6.0 Hz, 6H); MS: MS m/z 355.2 (M++1).

Workup

  1. customTo a 2 dram vial equipped with a stir bar
  2. customThe vial was sealed with a septum
  3. customscrew-cap
  4. additionTo the vial was added
  5. customdegassed DMF (1 mL)
  6. customwas placed in a 80° C.
  7. temperatureheating block
  8. customwas then directly purified via C18 chromatography (water:MeOH w/0.1% TFA)

Sources & evidence

ORD record
ord-1b7d81763f1d4f90aafef7b4a53da1c4
Source dataset
uspto-grants-2016_05
Patent number
US09334279B2

Linked notes

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