Pivalic acid → HCID 55273328, compound

HRID 1776163Notes

Reaction equation

[F:1][C:2]1[CH:14]=[CH:13][CH:12]=[CH:11][C:3]=1[NH:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.C(=O)([O-])[O-].[K+].[K+].C(O)(=O)C(C)(C)C>C(Cl)Cl.C([O-])(=O)C.C([O-])(=O)C.[Pd+2]>[F:1][C:2]1[C:3]2[NH:4][C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[C:11]=2[CH:12]=[CH:13][CH:14]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A reaction vessel was charged with 2-fluoro-N-phenylaniline (0.4 g, 2.1 mmol), palladium diacetate (0.025 g, 0.1 mmol), potassium carbonate (0.030 g, 0.21 mmol), and pivalic acid (1.8 g), placed under an oxygen balloon, and heated at 120° C. Additional portions of palladium diacetate (0.025 g, 0.1 mmol) were added at 48 hours and 72 hours, and the mixture was heated for 4 days. The cooled reaction mixture was diluted with methylene chloride, washed with saturated aqueous sodium carbonate, dried (anhydrous sodium sulfate), filtered through a pad of silica gel, and concentrated. The crude product was purified by silica gel column chromatography (5-30% methylene chloride in hexanes) to give the desired product as a white solid (0.181 g, 46%). 1H NMR (d6-DMSO, 300 MHz) δ 11.65 (s, 1H), 8.13-8.11 (dd, 1H, J=0.6, 7.5 Hz), 7.94-7.91 (d, 1H, J=7.8 Hz), 7.50-7.38 (m, 2H), 7.25-7.07 (m, 3H). HPLC analysis (C18, 5-95% acetonitrile in H2O+0.1% trifluoroacetic acid over 20 min: retention time, % area at 254 nm): 9.65 min, 100%.

Workup

temperaturethe mixture was heated for 4 days
customThe cooled reaction mixture
washwashed with saturated aqueous sodium carbonate
dry with materialdried (anhydrous sodium sulfate)
filtrationfiltered through a pad of silica gel
concentrationconcentrated
customThe crude product was purified by silica gel column chromatography (5-30% methylene chloride in hexanes)

Sources & evidence

ORD record: ord-2a0cf708ac7c46e2a56e63f84c649cee
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09265772B2

Reaction notes

Loading…