Potassium Carbonate → HCID 10046641, compound

HRID 2373501Notes

Reaction equation

HRID 2373501 reaction equation
[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13](Br)=[CH:14][CH:15]=2)[C:10]([C:18](=[O:22])[C:19]([OH:21])=[O:20])=[C:9]1[CH2:23]O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[K].[Cl:26][C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1.C(=O)([O-])[O-].[K+].[K+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCOCC1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([C:30]3[CH:31]=[CH:32][C:27]([Cl:26])=[CH:28][CH:29]=3)=[CH:14][CH:15]=2)[C:10]2[C:18](=[O:22])[C:19](=[O:20])[O:21][CH2:23][C:9]1=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 742994-Chlorophenylboronic acidHCID 5462222PotassiumHCID 21964311HCID 21964311, compound2×

Product 1

HCID 10046641HCID 10046641, compound

Reagents, catalysts & solvents 4

HCID 74236Tetrabutylammonium BromideCatalystHCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of [1-benzyl-5-bromo-2-(hydroxymethyl)-1H-indol-3-yl](oxo)acetic acid, potassium salt (3.15 g, 7.4 mmol), 4-chlorophenylboronic acid (1.74 g, 2.6 mmol), potassium carbonate (2.55 g, 13.7 mmol), palladium(II) acetate (0.032 g) and tetrabutylammonium bromide (2.4 g, 7.4 mmol) in 15% dioxane in water (45 mL) was stirred at 70° C. The reaction was monitored by TLC. After no [1-benzyl-5-bromo-2-(hydroxymethyl)-1H-indol-3-yl](oxo)acetic acid, was detected by TLC, the reaction was cooled down and solvent was decanted. The dark gum-like oil was partitioned between ethyl acetate and 10% aqueous HCl. The upper organic layer was separated, washed with water, and filtered. This filtrate was evaporated to give a solid. This solid was triturated with ethyl ether with stirring and dried in vacuum at 60° C. for 8 hours to afford the title compound as an off-white solid (0.77 g), m.p. 263-264° C. Mass spectrum (ESI, [M+H]+) m/z 402. 1H NMR (400 MHz, DMSO-d6) δ 8.19 (s, 1H), 7.71-7.67 (m, 3H), 7.63 (dd, 1H, J=8.66 and 1.83 Hz),), 7.49 (dd, 2H, J=8.54 and 1.95 Hz), 7.34-7.25 (m, 3H), 7.22 (d, 2H, J=7.46 Hz), 5.88 (s, 2H), and 5.52 ppm (s, 2H).

Workup

  1. temperaturethe reaction was cooled down
  2. customsolvent was decanted
  3. customThe dark gum-like oil was partitioned between ethyl acetate and 10% aqueous HCl
  4. customThe upper organic layer was separated
  5. washwashed with water
  6. filtrationfiltered
  7. customThis filtrate was evaporated
  8. customto give a solid
  9. customThis solid was triturated with ethyl ether
  10. stirringwith stirring
  11. customdried in vacuum at 60° C. for 8 hours

Sources & evidence

ORD record
ord-920c07b1aadf4fa0ae36ef2d9bd16c79
Source dataset
uspto-grants-2008_12
Patent number
US07459478B2

Reaction notes

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