Cesium carbonate → Methyl 3-[[5-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-2-methyl-benzoyl]amino]-2,4-dimethyl-benzoate

Participants

Reaction Conditions

Reaction Steps

To a solution of methyl 3-[(5-bromo-2-methyl-benzoyl)amino]-2,4-dimethyl-benzoate (0.5 g, 1.33 mmol), 1,4-dioxa-8-azaspiro(4.5)decane (228.34 mg, 1.59 mmol) and Cs2CO3 (1.3 g, 3.99 mmol) in 1,4-dioxane (10 ml) is added Pd(OAc)2 (29.84 mg, 132.89 μmol) followed by racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (82.75 mg, 132.89 μmol). The reaction mixture is purged with nitrogen for 10 minutes and then heated to 90° C. After 3 hours, very small amount of the product is formed. To the reaction mixture is added Pd(OAc)2 (29.84 mg, 132.89 μmol) followed by racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (82.75 mg, 132.89 μmol) and heated to 100° C. After 12 hours, the reaction is cooled to ambient temperature and diluted with water and extracted with EtOAc. The combined organic layers are washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue is purified by flash chromatography (silica gel) using 0-100% ethyl acetate in hexane to afford the title compound as a brown solid (0.26 g, 44.62%). Mass spectrum (m/z): 439.2 (M+1).

Provenance & Evidence