Cesium carbonate → Methyl 4-(4-chloro-2-fluorophenyl)-6-methylnicotinate

HRID 1398424Notes

Reaction equation

HRID 1398424 reaction equation
Cl[C:2]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][N:5]=[C:4]([CH3:12])[CH:3]=1.[Cl:13][C:14]1[CH:19]=[CH:18][C:17](B(O)O)=[C:16]([F:23])[CH:15]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.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:13][C:14]1[CH:19]=[CH:18][C:17]([C:2]2[C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][N:5]=[C:4]([CH3:12])[CH:3]=2)=[C:16]([F:23])[CH:15]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 4193595(4-Chloro-2-fluorophenyl)boronic acidHCID 20691977Methyl 4-chloro-6-methylpyridine-3-carboxylate

Product 1

HCID 86695958Methyl 4-(4-chloro-2-fluorophenyl)-6-methylnicotinateYield 43%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of methyl 4-chloro-6-methylnicotinate (660 mg, 3.56 mmol) and (4-chloro-2-fluorophenyl)boronic acid (620 mg, 3.56 mmol) in 1,4-dioxane (20 mL) was added cesium carbonate (3.48 g, 10.67 mmol). The reaction mixture was degassed with argon over a period of 5 min. Pd(Ph3P)4 (205 mg, 0.178 mmol) was added to the reaction mixture and heated to 80° C. for 16 h. The mixture was cooled to room temperature, diluted with water, and extracted with ethyl acetate (100 mL). The organic phase was washed with brine (2×50 mL), dried over Na2SO4, and concentrated under reduced pressure. The residue obtained was purified by silica gel chromatography to afford methyl 4-(4-chloro-2-fluorophenyl)-6-methylnicotinate (500 mg, 1.53 mmol, 43% yield) as a yellow liquid. LC/MS (ESI) m/e 280.0 [(M+H)+, calcd for C14H12ClFNO2 279.6]; LC/MS retention time (method C): tR=1.87 min.

Workup

  1. customThe reaction mixture was degassed with argon over a period of 5 min
  2. temperatureThe mixture was cooled to room temperature
  3. extractionextracted with ethyl acetate (100 mL)
  4. washThe organic phase was washed with brine (2×50 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe residue obtained
  8. customwas purified by silica gel chromatography

Sources & evidence

ORD record
ord-0607dbd49e8d4db4a7cd210e501b7876
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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