Sodium Carbonate → 5-(3-Chloro-phenyl)-3-methoxy-3-prop-1-ynyl-1,3-dihydro-indol-2-one

HRID 1936939Notes

Reaction equation

HRID 1936939 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2([O:15][CH3:16])[C:12]#[C:13][CH3:14].[Cl:17][C:18]1[CH:19]=[C:20](B(O)O)[CH:21]=[CH:22][CH:23]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(COC)OC.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>[Cl:17][C:18]1[CH:23]=[C:22]([C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[NH:7][C:6](=[O:11])[C:5]3([O:15][CH3:16])[C:12]#[C:13][CH3:14])[CH:21]=[CH:20][CH:19]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 2734323(3-Chlorophenyl)boronic acidHCID 120859375-Bromo-3-methoxy-3-prop-1-ynyl-1,3-dihydroindol-2-one

Product 1

HCID 99486505-(3-Chloro-phenyl)-3-methoxy-3-prop-1-ynyl-1,3-dihydro-indol-2-oneYield 15%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Procedure

5-bromo-3-methoxy-3-prop-1-ynyl-1,3-dihydroindol-2-one (0.56 g, 2.0 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.12 g, 0.10 mmol ) were stirred at room temperature in dimethoxyethane (22 cm3). After 15 min. 3-chlorophenylboronic acid (0.63 g, 4.0 mmol) and sodium carbonate (1.06 g, 10 mmol) in water (11 cm3) were added and the mixture heated under reflux. After 16 h, the mixture was cooled, poured into water and extracted with EtOAc (×3). The combined organic layers were washed with sodium hydroxide (1N, ×2), brine, dried (MgSO4) and evaporated. The residue was subjected to column chromatography (SiO2, EtOAc:hexane, gradient elution) and the product triturated with hexane to afford the title compound (0.095 g, 0.30 mmol, 15%) as a solid: mp.>190° C. (decomp.); (CDCl3) δ1.88 (s, 3H), 3.25 (s, 3H), 3.30 (s, 1H), 6.91 (d, 1H, J=8.1 Hz), 7.29-7.39 (m, 2H), 7.44-7.47 (m, 1H), 7.54-7.57 (m, 2H), 7.74 (d, 1H, J=1.7 Hz); MS (EI) m/z 311 (M+).

Workup

  1. temperaturethe mixture heated
  2. temperatureunder reflux
  3. waitAfter 16 h
  4. temperaturethe mixture was cooled
  5. extractionextracted with EtOAc (×3)
  6. washThe combined organic layers were washed with sodium hydroxide (1N, ×2), brine
  7. dry with materialdried (MgSO4)
  8. customevaporated
  9. washThe residue was subjected to column chromatography (SiO2, EtOAc:hexane, gradient elution)
  10. customthe product triturated with hexane

Sources & evidence

ORD record
ord-33b73df21ca14df6ab762d350557b7ab
Source dataset
uspto-grants-2002_05
Patent number
US06391907B1

Reaction notes

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