Methyl iodide → Methyl 6-(3-formyl-4-methoxy-2-methylphenyl)pyridine-2-carboxylate

HRID 873517Notes

Reaction equation

HRID 873517 reaction equation
[CH3:1][O:2][C:3]1[C:8]([CH:9]=[O:10])=[C:7]([CH3:11])[C:6](B2OC(C)(C)C(C)(C)O2)=[CH:5][CH:4]=1.Br[C:22]1[N:27]=[C:26]([C:28]([O:30][CH3:31])=[O:29])[CH:25]=[CH:24][CH:23]=1.C(=O)([O-])[O-].[Na+].[Na+].[Cl-].[NH4+].C(=O)([O-])[O-].[K+].[K+].CI>COCCOC.O.CN(C=O)C.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.CCCCCC>[CH:9]([C:8]1[C:7]([CH3:11])=[C:6]([C:22]2[N:27]=[C:26]([C:28]([O:30][CH3:31])=[O:29])[CH:25]=[CH:24][CH:23]=2)[CH:5]=[CH:4][C:3]=1[O:2][CH3:1])=[O:10]

Participants

12

Reactant 6

HCID 6328Methyl iodideHCID 10340Sodium CarbonateHCID 11430Potassium CarbonateHCID 25517Ammonium ChlorideHCID 16217886Methyl 6-bromopyridine-2-carboxylateHCID 130141572HCID 130141572, compound

Product 1

HCID 117700848Methyl 6-(3-formyl-4-methoxy-2-methylphenyl)pyridine-2-carboxylateYield 60%

Reagents, catalysts & solvents 5

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8058HexaneSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

A suspension of the 6-methoxy-2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzaldehyde produced in Example 4-1 (1.01 g, 3.66 mmol), methyl 6-bromopyridine-2-carboxylate (0.79 g, 3.66 mmol), sodium carbonate (1.16 g, 11.0 mmol), and tetrakis(triphenylphosphine)palladium(0) (0.21 g, 0.18 mmol) in 1,2-dimethoxyethane (20.2 ml) and water (8.8 ml) was prepared at room temperature, and the suspension thus prepared was then stirred at 90° C. for 7 hours. After air-cooling, an aqueous solution of ammonium chloride was added to the reaction solution, and the mixed solution was then extracted with dichloromethane 21 times. The organic layer thus obtained was dried over anhydrous sodium sulfate. The solvent was distilled away under reduced pressure, and the residue thus obtained was then dissolved in DMF (20.2 ml). Thereafter, potassium carbonate (1.21 g, 8.78 mmol) and methyl iodide (0.27 ml, 4.39 mmol) were added to the resulting solution, and the mixture thus obtained was then stirred at 40° C. for 4 hours. After air-cooling, water was added to the reaction solution, and the mixed solution was then extracted with ethyl acetate. The organic layer thus obtained was washed with water, and was then dried over anhydrous sodium sulfate. The solvent was distilled away under reduced pressure, and the residue thus obtained was then purified by silica gel column chromatography (ethyl acetate:hexane=40:60, v/v) to obtain the title compound (0.625 g, yield: 60%).

Workup

  1. customwas prepared at room temperature
  2. customthe suspension thus prepared
  3. temperatureAfter air-cooling
  4. extractionthe mixed solution was then extracted with dichloromethane 21 times
  5. customThe organic layer thus obtained
  6. dry with materialwas dried over anhydrous sodium sulfate
  7. distillationThe solvent was distilled away under reduced pressure
  8. customthe residue thus obtained
  9. customthe mixture thus obtained
  10. stirringwas then stirred at 40° C. for 4 hours
  11. temperatureAfter air-cooling
  12. extractionthe mixed solution was then extracted with ethyl acetate
  13. customThe organic layer thus obtained
  14. washwas washed with water
  15. dry with materialwas then dried over anhydrous sodium sulfate
  16. distillationThe solvent was distilled away under reduced pressure
  17. customthe residue thus obtained
  18. customwas then purified by silica gel column chromatography (ethyl acetate

Sources & evidence

ORD record
ord-4ef14b65908f420383261c7553b485f1
Source dataset
uspto-grants-2015_03
Patent number
US08975263B2

Reaction notes

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