Potassium Carbonate → 5-(3-Chloro-4-fluoro-phenyl)-3,3-dimethyl1,3-dihydro-indol-2-one

HRID 1936950

Reaction equation

HRID 1936950 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([CH3:13])[CH3:12].[Cl:14][C:15]1[CH:16]=[C:17](B(O)O)[CH:18]=[CH:19][C:20]=1[F:21].C(=O)([O-])[O-].[K+].[K+].[Cl-].[NH4+]>C(COC)OC.O.[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>[Cl:14][C:15]1[CH:16]=[C:17]([C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[NH:7][C:6](=[O:11])[C:5]3([CH3:13])[CH3:12])[CH:18]=[CH:19][C:20]=1[F:21]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 25517Ammonium ChlorideHCID 27346603-Chloro-4-fluorophenylboronic Acid (contains varying amounts of Anhydride)HCID 120527965-bromo-3,3-dimethyl-2,3-dihydro-1H-indol-2-one

Product 1

HCID 98607755-(3-Chloro-4-fluoro-phenyl)-3,3-dimethyl1,3-dihydro-indol-2-oneYield 30%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A solution of 5-bromo-3,3-dimethyl-1,3-dihydro-indol-2-one (0.35 g, 1.46 mmol) and tetrakis(triphenylphosphine) palladium (0.13 g, 0.11 mmol) in dimethoxyethane (10 cm3) was stirred under N2 for 20 min. To this mixture was then added 3-chloro-4-fluorobenzene boronic acid (0.26 g, 1.49 mmol) and potassium carbonate (0.62 g, 4.5 mmol) in water (5 cm3). The solution was brought to reflux for 16 h then cooled to RT, poured into saturated ammonium chloride and extracted with EtOAc (×3). The combined organic extracts were dried (MgSO4), and evaporated. The residue was purified by column chromatography (SiO2, ethyl acetate: hexane 1:3) to afford the title compound (0.124 g, 0.43 mmol, 30%) as a white solid: mp. 206.5-207.8° C., 1H NMR (DMSO-d6) δ1.3 (s, 6H), 6.93 (d, J=8.1 Hz, 1H), 7.45 (dd, J=8.9, 8.9 Hz, 1H), 7.5 (dd, J=8.1, 1.8 Hz, 1H), 7.6 (ddd, J=8.9, 7.1, 2.2 Hz, 1H), 7.7 (d, J=1.8 Hz, 1H), 7.8 (dd, J=7.1, 2.2 Hz, 1H), 10.5 (s, 1H); MS (EI) m/z 289/291 (M)+.

Workup

  1. temperatureto reflux for 16 h
  2. extractionextracted with EtOAc (×3)
  3. dry with materialThe combined organic extracts were dried (MgSO4)
  4. customevaporated
  5. customThe residue was purified by column chromatography (SiO2, ethyl acetate: hexane 1:3)

Sources & evidence

ORD record
ord-c16339837d1a44ae9a80fa833af6f393
Source dataset
uspto-grants-2002_05
Patent number
US06391907B1

Linked notes

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