Cesium carbonate → 3-chloro-2-methoxy-6-[(E)-1-[4-(propan-2-yl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethenyl]pyridine

HRID 70611

Reaction equation

HRID 70611 reaction equation
[CH:1]([C:4]1[CH:9]=[CH:8][C:7](B(O)O)=[CH:6][CH:5]=1)([CH3:3])[CH3:2].O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br/[C:36](/[C:44]1[N:49]=[C:48]([O:50][CH3:51])[C:47]([Cl:52])=[CH:46][CH:45]=1)=[CH:37]\[CH:38]1[CH2:43][CH2:42][O:41][CH2:40][CH2:39]1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[Cl:52][C:47]1[C:48]([O:50][CH3:51])=[N:49][C:44](/[C:36](/[C:7]2[CH:8]=[CH:9][C:4]([CH:1]([CH3:3])[CH3:2])=[CH:5][CH:6]=2)=[CH:37]/[CH:38]2[CH2:43][CH2:42][O:41][CH2:40][CH2:39]2)=[CH:45][CH:46]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 521585Tris(furan-2-yl)phosphaneHCID 27734804-Isopropylphenylboronic acidHCID 584525136-[(Z)-1-bromo-2-(tetrahydro-2H-pyran-4-yl)ethenyl]-3-chloro-2-methoxypyridine

Product 1

HCID 673964093-chloro-2-methoxy-6-[(E)-1-[4-(propan-2-yl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethenyl]pyridine

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

4-Isopropylphenylboronic acid (103 mg), tris(dibenzylideneacetone)dipalladium (38 mg), tri(2-furyl)phosphine (58 mg), cesium carbonate (273 mg) and water (0.5 mL) were added to a solution of 6-[(Z)-1-bromo-2-(tetrahydro-2H-pyran-4-yl)ethenyl]-3-chloro-2-methoxypyridine (140 mg) in 1,4-dioxane (3 mL), and the mixture was stirred at 90° C. for two hours. The reaction solution was poured into water, followed by extraction with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and filtered. The solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1→1:1) to give 3-chloro-2-methoxy-6-[(E)-1-[4-(propan-2-yl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethenyl]pyridine containing impurities as a yellow oil (170 mg).

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. customThe solvent was then evaporated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1→1:1)

Sources & evidence

ORD record
ord-a7091b02514d44df8b669a8650c38874
Source dataset
uspto-grants-2014_09
Patent number
US08822503B2

Linked notes

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