18-Crown-6 → tert-Butyl 4-(3-chloro-4-cyanoisothiazol-5-yl)phenylcarbamate

Participants

Reaction Steps

A mixture of 3,5-dichloroisothiazole-4-carbonitrile (5.37 g, 30 mmol), 4-(tertbutoxycarbonylamino)phenylboronic acid (14.22 g, 60 mmol), potassium fluoride (6.11 g, 105 mmol), 18-crown-6 (3.96 g, 15 mmol), and palladium acetate (337 mg, 1.5 mmol) in toluene (250 ml) was heated at reflux for 6 hours. The reaction was cooled to RT and the mixture was diluted with water and EtOAc. Layers were separated and the aqueous layer was extracted with EtOAc×3. The combined organics was washed with brine and dried with MgSO4, filtered, and concentrated. The crude product was purified by flash silica gel column eluted with 5-15% EtOAc in hexanes to obtain the above compound as a white crystalline solid (8.55 g, 85%). NMR and MS spectra are consistent with the structure. HPLC purity 97.6%.

Provenance & Evidence