Sodium Carbonate → Methanone, [2-[4-(methylthio)phenyl]-3-pyridinyl]-2-pyridinyl-

HRID 1295834Notes

Reaction equation

HRID 1295834 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]([C:9]1[C:10](Cl)=[N:11][CH:12]=[CH:13][CH:14]=1)=[O:8].[CH3:16][S:17][C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][CH:19]=1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.O>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]([C:9]1[C:10]([C:21]2[CH:22]=[CH:23][C:18]([S:17][CH3:16])=[CH:19][CH:20]=2)=[N:11][CH:12]=[CH:13][CH:14]=1)=[O:8]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27339594-(Methylthio)phenylboronic acidHCID 23284547(2-Chloropyridin-3-yl)(pyridin-2-yl)methanone

Product 1

HCID 11208980Methanone, [2-[4-(methylthio)phenyl]-3-pyridinyl]-2-pyridinyl-Yield 68%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

2-Chloro(3-pyridyl) 2-pyridyl ketone (Ryan Scientific Inc., South Carolina, U.S.) (810 mg, 3.7 mmol) and 4-(methylthio)benzeneboronic acid (830 mg, 5 mmol) were dissolved in toluene (50 mL) and ethanol (5 mL). To this solution was added 2 M Na2CO3 (6 mL, 12 mmol) followed by tetrakis (triphenylphosphine)palladium (250 mg, 0.2 mmol) and the resulting mixture was refluxed overnight under nitrogen atmosphere. The mixture was then cooled to room temperature and diluted with water (25 mL), stirred and the aqueous layer was separated and extracted with ethyl acetate (1×75 mL). The combined organic layers were washed with water (2×50 mL), brine (1×50 mL), dried over sodium sulfate, filtered and concentrated at reduced pressure to give the crude product. Purification by column chromatography over silica gel using 40% ethyl acetate in hexane gave the title compound (770 mg, 68% yield) as a white solid; mp 122-123° C.; 1H NMR (CDCl3) δ 8.87 (dd, J=4.8 and 1.7 Hz, 1H), 8.45 (d, J=4.7 Hz, 1H), 8.0 (dd, J=7.7 and 1.4 Hz, 2H), 7.75 (m, 1H), 7.45-7.3 (m, 4H), 7.12 (d, J=8.4 Hz, 2H), 2.44 (s, 3H); 13C NMR (CDCl3) δ 196.0, 157.6, 153.5, 150.7, 148.8, 139.3, 137.4, 136.6, 136.5, 133.6, 129.4 (2C), 126.5, 125.7 (2C), 123.5, 121.1, 15.3; LRMS (APIMS) m/z 307 (M+H)+.

Workup

  1. temperaturethe resulting mixture was refluxed overnight under nitrogen atmosphere
  2. customthe aqueous layer was separated
  3. extractionextracted with ethyl acetate (1×75 mL)
  4. washThe combined organic layers were washed with water (2×50 mL), brine (1×50 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated at reduced pressure
  8. customto give the crude product
  9. customPurification by column chromatography over silica gel using 40% ethyl acetate in hexane

Sources & evidence

ORD record
ord-0e58f9836d674cfe85b2093dcda75c4b
Source dataset
uspto-grants-2007_07
Patent number
US07244753B2

Reaction notes

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