Cesium carbonate → 2-Chloro-5-(6-methyl-pyridin-3-yl)-benzoic acid methyl ester

HRID 1988365Notes

Reaction equation

HRID 1988365 reaction equation
[CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:9]=[C:8](B2OC(C)(C)C(C)(C)O2)[CH:7]=[CH:6][C:5]=1[Cl:19].[C:21](=O)([O-])[O-].[Cs+].[Cs+].Cl[C:28]1[CH:33]=[CH:32][C:31](C)=[CH:30][N:29]=1>O1CCOCC1.C(#N)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:9]=[C:8]([C:31]2[CH:30]=[N:29][C:28]([CH3:21])=[CH:33][CH:32]=2)[CH:7]=[CH:6][C:5]=1[Cl:19]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 5813932-Chloro-5-methyl-pyridine2×HCID 56972886Benzoic acid, 2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-, methyl ester

Product 1

HCID 588181752-Chloro-5-(6-methyl-pyridin-3-yl)-benzoic acid methyl esterYield 31.5%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalyst2×HCID 6342AcetonitrileSolventHCID 312751,4-DioxaneSolvent

Procedure

To a mixture of 2-chloro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid methyl ester (628 mg, 2.12 mmol), cesium carbonate (1.38 g, 4.25 mmol), tetrakis(triphenylphosphine) palladium (62 mg, 0.08 mmol) and molecular sieves (2 g, 4 Å) in 1,4-dioxane (10 mL) was added 2-chloro-5-methylpyridine (226 mg, 1.77 mmol). The mixture was stirred for a few minutes at room temperature then warmed to 80° C. for 4 h. A further portion of tetrakis(triphenylphosphine) palladium (120 mg, 0.10 mmol) was added and the resulting mixture was stirred at 80° C. for 16 h. A second portion of 2-chloro-5-methylpyridine (117 mg, 0.66 mmol) was added. The resulting mixture was stirred at 80° C. for a further 5 h. The reaction mixture was diluted with acetonitrile (30 mL) and filtered through a pad of celite. The filtrate was concentrated in vacuo and purified by flash column chromatography (gradient 5-100% ethyl acetate-hexane) to afford the title compound (146 mg).

Workup

  1. temperaturethen warmed to 80° C. for 4 h
  2. stirringthe resulting mixture was stirred at 80° C. for 16 h
  3. stirringThe resulting mixture was stirred at 80° C. for a further 5 h
  4. filtrationfiltered through a pad of celite
  5. concentrationThe filtrate was concentrated in vacuo
  6. custompurified by flash column chromatography (gradient 5-100% ethyl acetate-hexane)

Sources & evidence

ORD record
ord-bedef284b586413c89e213f67327ed12
Source dataset
uspto-grants-2009_06
Patent number
US07553972B2

Reaction notes

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