Potassium Carbonate → 3-(4-Fluoro-phenyl)-7-hydroxy-4-methyl-thieno[3,2-c]pyridine-6-carboxylic acid methyl ester

HRID 1465954Notes

Reaction equation

HRID 1465954 reaction equation
[CH3:1][O:2][C:3]([C:5]1[N:10]=[C:9](Br)[C:8]2[C:12]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)=[CH:13][S:14][C:7]=2[C:6]=1[OH:22])=[O:4].[CH3:23]C1(C)CCCB(C)O1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.C(OCC)(=O)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]([C:5]1[N:10]=[C:9]([CH3:23])[C:8]2[C:12]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)=[CH:13][S:14][C:7]=2[C:6]=1[OH:22])=[O:4]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 22327867TrimethylboroxaneHCID 866075134-Bromo-3-(4-fluoro-phenyl)-7-hydroxy-thieno[3,2-c]pyridine-6-carboxylic acid methyl ester

Product 1

HCID 672338603-(4-Fluoro-phenyl)-7-hydroxy-4-methyl-thieno[3,2-c]pyridine-6-carboxylic acid methyl esterYield 56.8%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Under a nitrogen atmosphere, a mixture of 4-bromo-3-(4-fluoro-phenyl)-7-hydroxy-thieno[3,2-c]pyridine-6-carboxylic acid methyl ester (77.9 mg, 0.204 mmol), example 32-a, trimethylboroxane (57.0 μL, 0.408 mmol), potassium carbonate (169 mg, 1.22 mmol), and tetrakis(triphenylphosphine)-palladium(0) (35.3 mg, 0.031 mmol) were suspended in 3.5 mL of anhydrous 1,4-dioxane. The reaction mixture was heated at 100° C. for 16 hours, cooled to room temperature, and diluted with ethyl acetate. The organic mixture was successively washed with water, saturated sodium bicarbonate, and brine solutions. The organic fractions were dried over anhydrous sodium sulfate and concentrated. The crude product was purified by flash chromatography eluting from silica gel with a gradient of 0-50% ethyl acetate in hexanes to produce 36.8 mg of a white solid. MS: (+) m/z 318.0 (M+1).

Workup

  1. temperaturecooled to room temperature
  2. washThe organic mixture was successively washed with water, saturated sodium bicarbonate, and brine solutions
  3. dry with materialThe organic fractions were dried over anhydrous sodium sulfate
  4. concentrationconcentrated
  5. customThe crude product was purified by flash chromatography
  6. washeluting from silica gel with a gradient of 0-50% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-700fd3cb2e224ab79ab65eb47b8cdafe
Source dataset
uspto-grants-2015_04
Patent number
US09000006B2

Reaction notes

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