Potassium Carbonate → HCID 21964293, compound

HRID 2373484Notes

Reaction equation

HRID 2373484 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([CH2:11][OH:12])=[CH:5]2.[CH3:13][C:14]1[CH:15]=[C:16](B(O)O)[CH:17]=[CH:18][CH:19]=1.C(=O)([O-])[O-].[K+].[K+].BrC1C=C2C(=CC=1)N(CC1C=CC(C(C)(C)C)=CC=1)C=C2>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCOCC1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:13][C:14]1[CH:19]=[C:18]([C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[NH:7][C:6]([CH2:11][OH:12])=[CH:5]3)[CH:17]=[CH:16][CH:15]=1

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 27339503-Tolylboronic acid2×HCID 13567955(5-Bromo-1H-indol-2-yl)methanolHCID 21964287HCID 21964287, compound

Product 1

HCID 21964293HCID 21964293, compoundYield 63.5%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
70 °C

Procedure

A mixture of (5-bromo-1H-indol-2-yl) methanol (9 g, 39.8 mmol), 3-methylbenzeneboronic acid (6.14 g, 43.78 mmol), potassium carbonate (13.75 g, 99.5 mmol), palladium(II) acetate (0.045 g) and tetrabutylammonium bromide (12.84 g, 39.8 mmol) in 10% dioxane in water (degassed, 0.38 L) was stirred at 70° C. The reaction was monitored by TLC. Additional 3-methylbenzeneboronic acid (5.6 g, 39.8 mmol) was added. After no 5-bromo-1-(4-tert-butylbenzyl)-1H-indole was detected by TLC, the reaction was cooled to room temperature and the solvent was decanted. The residual thick oil was stirred with hexane. The hexane was decanted and the residue was partitioned between water and ethyl acetate. The ethyl acetate layer was separated, washed with water filtered and concentrated. The residue was purified by flash column chromatography using hexane/ethyl acetate (55:45) as an eluant to give [5-(3-Methylphenyl)-1H-indol-2-yl]methanol as a brown solid (6.0 g). Reaction of [5-(3-Methylphenyl)-1H-indol-2-yl]methanol with acetyl chloride according to the procedure described in step 4 of Example 1 afforded the title compound as an oil (3.94 g); Mass spectrum (ESI, [M−H]−) m/z 278. 1H NMR (400 MHz, DMSO-d6) δ 7.76 (s, 1H), 7.46 (s, 1H), 7.42-7.36 (m, 3H), 7.30 (s, 1H), 7.10 (d, 1H, J=7.48 Hz), 6.50 (s, 1H), 2.37 (s, 3H), and 2.07 ppm (s, 3H).

Workup

  1. temperaturethe reaction was cooled to room temperature
  2. customthe solvent was decanted
  3. stirringThe residual thick oil was stirred with hexane
  4. customThe hexane was decanted
  5. customthe residue was partitioned between water and ethyl acetate
  6. customThe ethyl acetate layer was separated
  7. washwashed with water
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-4c3876b9a12e41d58fd83badd8708aa8
Source dataset
uspto-grants-2008_12
Patent number
US07459478B2

Reaction notes

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