Potassium Carbonate → HCID 22032964, compound

HRID 1791462Notes

Reaction equation

HRID 1791462 reaction equation
[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13](Br)=[CH:14][CH:15]=2)[CH:10]=[CH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:18][C:19]([F:31])([F:30])[O:20][C:21]1[CH:22]=[C:23](B(O)O)[CH:24]=[CH:25][CH:26]=1.C(=O)([O-])[O-].[K+].[K+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O.C1COCC1.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:23]3[CH:24]=[CH:25][CH:26]=[C:21]([O:20][C:19]([F:18])([F:30])[F:31])[CH:22]=3)=[CH:14][CH:15]=2)[CH:10]=[CH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 2857561-Benzyl-5-Bromo-1H-IndoleHCID 27343853-(Trifluoromethoxy)phenylboronic Acid (contains varying amounts of Anhydride)

Product 1

HCID 22032964HCID 22032964, compoundYield 38%

Reagents, catalysts & solvents 4

HCID 74236Tetrabutylammonium BromideCatalystHCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

1-Benzyl-5-[3-(trifluoromethoxy)phenyl]-1H-indole was prepared by coupling 1-benzyl-5-bromo-1H-indole (2.28 g, 7.97 mmol), and 3-(trifluoromethoxy)phenylboronic acid (1.66 g, 8.06 mmol), using potassium carbonate (2.75, 19.9 mmol), palladium(II) acetate (0.0731 g, 0.326 mmol), and tetrabutylammonium bromide (2.78 g, 8.62 mmol) in water (45 mL) and THF (5 mL), according to the procedure described in Step 1 of Example 21. Following work-up the residue was purified by reverse phase HPLC using 81% acetonitrile and 0.1% TFA in water as the mobile phase. Evaporation of the acetonitrile, extraction of the aqueous phase with ethyl acetate, and evaporation to dryness afforded the title compound as an orange solid (1.10 g, 38%), mp: 62-65° C. Mass spectrum (+ESI, [M+H]+) m/z 368.5; 1HNMR (500 MHz, DMSO-d6): δ 7.9 (s, 1H), 7.7 (m, 1H), 7.5-7.6 (m, 4H), 7.45 (dd, 1H, J=8.6 Hz and 1.8 Hz), 7.2-7.3 (m, 6H), 6.55 (m, 1H), and 5.45 ppm (s, 1H).

Workup

  1. custom1-Benzyl-5-[3-(trifluoromethoxy)phenyl]-1H-indole was prepared
  2. customwas purified by reverse phase
  3. customEvaporation of the acetonitrile, extraction of the aqueous phase
  4. customwith ethyl acetate, and evaporation to dryness

Sources & evidence

ORD record
ord-1fe7703d3aa2480d97d9b92cefa78595
Source dataset
uspto-grants-2006_07
Patent number
US07074817B2

Reaction notes

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