Dimethylformamide → Methyl 3-{[5-(5-formylpyrazin-2-yl)-4-methylpyridin-2-yl]oxy}-2,2-dimethylpropanoate

HRID 623903Notes

Reaction equation

HRID 623903 reaction equation
CN(C)C=O.Cl[C:7]1[N:8]=[CH:9][C:10]([CH:13]=[O:14])=[N:11][CH:12]=1.[CH3:15][C:16]([CH3:39])([CH2:21][O:22][C:23]1[CH:28]=[C:27]([CH3:29])[C:26](B2OC(C)(C)C(C)(C)O2)=[CH:25][N:24]=1)[C:17]([O:19][CH3:20])=[O:18].C(=O)([O-])[O-].[Na+].[Na+]>O.C(OCC)(=O)C>[CH:13]([C:10]1[N:11]=[CH:12][C:7]([C:26]2[C:27]([CH3:29])=[CH:28][C:23]([O:22][CH2:21][C:16]([CH3:15])([CH3:39])[C:17]([O:19][CH3:20])=[O:18])=[N:24][CH:25]=2)=[N:8][CH:9]=1)=[O:14]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 216980675-Chloropyrazine-2-carbaldehydeHCID 67975267Methyl 2,2-dimethyl-3-((4-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)pyridin-2-yl)oxy)propanoate

Product 1

HCID 86698176Methyl 3-{[5-(5-formylpyrazin-2-yl)-4-methylpyridin-2-yl]oxy}-2,2-dimethylpropanoateYield 74%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

N,N-dimethylformamide (10 mL) was added to 5-chloropyrazine-2-carbaldehyde (500 mg), methyl 2,2-dimethyl-3-{[4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]oxy}propanoate (1410 mg) and 2N aqueous sodium carbonate solution (5.26 mL), and after replacing the atmosphere with nitrogen, palladium chloride (dppf) methylene chloride complex (143 mg) was added to the mixture and the resulting mixture was stirred at 65° C. for 2 hours. To the reaction mixture were added ethyl acetate and water, and the liquids were separated. After filtration with Celite, the organic layer was separated, washed with water and then with a saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=100:0 to 70:30) to obtain methyl 3-{[5-(5-formylpyrazin-2-yl)-4-methylpyridin-2-yl]oxy}-2,2-dimethylpropanoate (855 mg).

Workup

  1. additionwas added to the mixture
  2. customthe liquids were separated
  3. filtrationAfter filtration with Celite
  4. customthe organic layer was separated
  5. washwashed with water
  6. dry with materialwith a saturated brine, dried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe obtained residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=100:0 to 70:30)

Sources & evidence

ORD record
ord-d674b7f94799496d94a50e7428a47345
Source dataset
uspto-grants-2016_04
Patent number
US09302996B2

Reaction notes

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