Toluene → 3-(4-chloro-6,7-dihydro-5H-cyclopenta[b]pyridin-2-yl)cyclopent-2-enone

HRID 1508800Notes

Reaction equation

HRID 1508800 reaction equation
Cl[C:2]1[N:7]=[C:6]2[CH2:8][CH2:9][CH2:10][C:5]2=[C:4]([Cl:11])[CH:3]=1.CC1(C)C(C)(C)OB([C:20]2[CH2:24][CH2:23][C:22](=[O:25])[CH:21]=2)O1.C([O-])([O-])=O.[Cs+].[Cs+].C1(C)C=CC=CC=1>C(OCC)(=O)C.O.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.CCO>[Cl:11][C:4]1[CH:3]=[C:2]([C:20]2[CH2:24][CH2:23][C:22](=[O:25])[CH:21]=2)[N:7]=[C:6]2[CH2:8][CH2:9][CH2:10][C:5]=12

Participants

9

Reactant 4

HCID 1140TolueneHCID 10796Cesium carbonateHCID 122148172,4-Dichloro-6,7-dihydro-5H-cyclopenta[b]pyridineHCID 668228763-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-2-cyclopenten-1-one

Product 1

HCID 1180370593-(4-chloro-6,7-dihydro-5H-cyclopenta[b]pyridin-2-yl)cyclopent-2-enoneYield 23.4%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

A 250-mL round bottomed flask was charged with 2,4-dichloro-6,7-dihydro-5H-cyclopenta[b]pyridine (1.05 g, 5.58 mmol), 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclopent-2-enone (1.27 g, 6.14 mmol), tetrakis(triphenylphosphine)palladium(0) (0.322 g, 0.28 mmol), and Cs2CO3 (5.45 g, 16.7 mmol). Toluene (30 ml), EtOH (7.5 ml) and water (15 ml) were added. The resulting mixture was stirred under argon at 90° C. for 18 h. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate (150 mL), hexanes (50 mL) and water (25 mL). The aqueous layer was separated and extracted with ethyl acetate (2×100 mL). The combined organic extract was washed with saturated sodium chloride (2×20 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on silica using hexane/ethyl acetate (10:0 to 0:10) as eluent to afford the title compound (0.305 g, 23%) as a yellow solid. MW=233.69. 1H NMR (CDCl3, 500 MHz) δ 7.41 (s, 1H), 6.79 (t, J=2.0 Hz, 1H), 3.13 (t, J=7.5 Hz, 2H), 3.10-3.06 (m, 2H), 3.04 (t, J=7.5 Hz, 2H), 2.62-2.58 (m, 2H), 2.20 (quin, J=7.5 Hz, 2H).

Workup

  1. temperatureAfter cooling to room temperature
  2. customThe aqueous layer was separated
  3. extractionextracted with ethyl acetate (2×100 mL)
  4. extractionThe combined organic extract
  5. washwas washed with saturated sodium chloride (2×20 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by chromatography on silica

Sources & evidence

ORD record
ord-0889d7194d6a480fbe478354554bcd75
Source dataset
uspto-grants-2015_12
Patent number
US09221843B2

Reaction notes

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