Sodium Carbonate → 6-(4-FLUOROPHENYL)INDOLE

HRID 1811033Notes

Reaction equation

Br[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][NH:8]2)=[CH:4][CH:3]=1.[F:11][C:12]1[CH:17]=[CH:16][C:15](B(O)O)=[CH:14][CH:13]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.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>[F:11][C:12]1[CH:17]=[CH:16][C:15]([C:2]2[CH:10]=[C:9]3[C:5]([CH:6]=[CH:7][NH:8]3)=[CH:4][CH:3]=2)=[CH:14][CH:13]=1

Participants

Conditions

Temperature: 90 °C

Procedure

Step 1 A mixture of 6-bromo-1H-indole (0.25 g, 1.275 mmol), 4-fluorophenylboronic acid (0.178 g, 1.275 mmol), and 2 M aqueous sodium carbonate (2.0 mL, 4.00 mmol) in toluene (10 mL) and ethanol (2.500 mL) was purged with argon and treated with tetrakis(triphenylphosphine)palladium (0.074 g, 0.064 mmol). The mixture was heated at 90° C. After 17 h, the mixture was cooled to rt and partitioned between water and EtOAc. The organic phase was dried and concentrated. The residue was purified by column chromatography (eluting with a gradient from 95:5 to 60:40 hexane-EtOAc) to provide 6-(4-fluorophenyl)-1H-indole as a white solid (175.5 mg, 65%). 1H NMR (400 MHz, DMSO-d6) δ 11.17 (1 H, br. s.), 7.65-7.71 (2 H, m), 7.56-7.62 (2 H, m), 7.37 (1 H, t, J=2.9 Hz), 7.22-7.31 (3 H, m), 6.44 (1 H, t, J=2.0 Hz). Mass spectrum m/z 212.2 (M+H)+.

Workup

customwas purged with argon
temperaturethe mixture was cooled to rt
custompartitioned between water and EtOAc
customThe organic phase was dried
concentrationconcentrated
customThe residue was purified by column chromatography (
washeluting with a gradient from 95:5 to 60:40 hexane-EtOAc)

Sources & evidence

ORD record: ord-f7b6effe5b9f4c3090b8ce544423651a
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08362065B2

Reaction notes

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