Water → HCID 86680487, compound

HRID 1497474Notes

Reaction equation

HRID 1497474 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.O.[C:11]([C:14]1[S:18][C:17](B(O)O)=[CH:16][CH:15]=1)(=[O:13])[CH3:12].C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:11]([C:14]1[S:18][C:17]([C:2]2[CH:3]=[CH:4][C:5](=[O:9])[N:6]([CH3:8])[CH:7]=2)=[CH:16][CH:15]=1)(=[O:13])[CH3:12]

Participants

8

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 4143377(5-Acetylthiophen-2-yl)boronic acidHCID 130240275-Bromo-1-methylpyridin-2(1H)-one

Product 1

HCID 86680487HCID 86680487, compoundYield 52.5%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 5-bromo-1-methylpyridin-2(1H)-one (1.0 g, 5.31 mmol) in 1,4-dioxane (10 mL)\H2O (5 mL) was added 5-acetylthiophen-2-yl boronic acid (1.35 g, 7.97 mmol), tetra-butyl ammonium bromide (17 mg, 0.053 mmol), K2CO3 (2.19 g, 15.93 mmol) and Pd(PPh3)2Cl2 (37 mg, 0.053 mmol) under argon. The mixture was degassed and heated to 100° C. for 3 h. After the reaction was complete based on monitoring by TLC (80% EtOAc\hexane), the mixture was filtered with Celite® reagent and the filtrate was separated. This filtrate was concentrated and extracted with EtOAc (2×100 mL), washed with water (100 mL), and brine solution (100 mL). The organic layer was dried over sodium sulphate and concentrated in vacuum. The residue was purified by Combiflash® column purifier (80% ethyl acetate in hexane) to provide 5-(5-acetylthiophen-2-yl)-1-methylpyridin-2(1H)-one as a yellow viscous liquid (0.65 g, 43% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.31 (d, 1H), 7.88 (d, 1H), 7.80 (dd, 1H), 7.41 (d, 1H), 6.46 (d, 1H), 3.48 (s, 3H), 2.48 (s, 3H); LC-MS m/z calcd for [M+H]+ 234.05. found 234.1.

Workup

  1. customThe mixture was degassed
  2. filtrationthe mixture was filtered with Celite® reagent
  3. customthe filtrate was separated
  4. concentrationThis filtrate was concentrated
  5. extractionextracted with EtOAc (2×100 mL)
  6. washwashed with water (100 mL), and brine solution (100 mL)
  7. dry with materialThe organic layer was dried over sodium sulphate
  8. concentrationconcentrated in vacuum
  9. customThe residue was purified by Combiflash® column purifier (80% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-0261bbb861d14a56b3df78c470847195
Source dataset
uspto-grants-2015_12
Patent number
US09199975B2

Reaction notes

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