Ethyl Acetate → Benzoyl isocyanate

Participants

Reaction Conditions

Reaction Steps

3-Bromo-5,7,8,9-tetrahydro-6-oxa-1,9-diaza-benzocycloheptene (78 mg, 0.34 mmol), 3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-5-trifluoromethyl-pyridine (190 mg, 0.68 mmol) and K2CO3 (94 mg, 0.68 mmol) are mixed in 5.0 mL of 1,4-dioxane and 0.50 mL of water. Argon gas is bubbled through the mixture for 10 min and bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium (II) (24 mg, 0.034 mmol) is added. The mixture is heated at 100° C. for 5 hrs. Then EtOAc (25 mL) is added along with 20 mL of water. The mixture is stirred for 10 min and the organic layer is separated. The aqueous layer is extracted with EtOAc (2×25 mL) and the organic layers are combined and concentrated to give the crude product. Purification by flash column chromatography affords 96 mg of 3-(5-trifluoromethyl-pyridin-3-yl)-5,7,8,9-tetrahydro-6-oxa-1,9-diaza-benzocycloheptene 3-(5-Trifluoromethyl-pyridin-3-yl)-5,7,8,9-tetrahydro-6-oxa-1,9-diaza-benzocycloheptene (96 mg, 0.33 mmol) and benzoyl isocyanate (80 mg, 0.49 mmol) are mixed in 2.0 mL of DCM and the mixture is heated at 50° C. for 16 hrs. Then the solvent is removed and the residue is dissolved in 2.0 mL of EtOH. K2CO3 (76 mg, 0.55 mmol) is added and the mixture is heated at 80° C. for 2 hrs. Then the solvent is removed and the residue is partitioned between water (25 mL) and EtOAc (35 mL). The aqueous layer is separated and extracted with EtOAc (2×30 mL). The organic layers are combined and concentrated to give the crude product. Purification by flash column chromatography followed by washing with 2.0 mL of EtOAc affords 47 mg of the titled product.

Provenance & Evidence