Methyl chloroformate → HCID 118389629, compound

Participants

Reaction Conditions

Reaction Steps

A solution of methyl 2-[3-bromo-4-(3,4-dihydro-2H-1-benzopyran-6-yl)-1-methyl-1H-pyrazol-5-yl]-2-(tert-butoxy)acetate (11i) (100 mg, 0.229 mmol), disodium carbonate (73 mg, 0.686 mmol), and 3-(tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-2-en-1-one (43b) (51 mg, 0.229 mmol) in a mixture of dimethoxyethane (0.87 mL), ethanol (0.37 mL) and water (0.25 mL) was bubbled with nitrogen for 5 minutes. [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (9.3 mg, 0.011 mmol) was added and the reaction mixture was heated at 140° C. for 2 hours. The solution was concentrated in vacuo. Water (2 mL) was added to the residue and the aqueous layer was washed with diethyl ether (2 mL), acidified with 1M hydrochloric acid until pH 3 and extracted with diethyl ether (2×3 mL). The organic layer was dried over sodium sulfate and concentrated in vacuo. The crude was dissolved in dichloromethane (1 mL), cooled to 0° C., and under a nitrogen atmosphere, triethylamine (48 μL, 0.343 mmol) and methyl chloroformate (27 μL, 0.343 mmol) were added. The reaction mixture was stirred at 0° C. for 40 minutes and allowed to reach room temperature. Dichloromethane (2 mL) was added, and the mixture was successively washed with 1N hydrochloric acid (2 mL), a saturated solution of sodium hydrogenocarbonate (2 mL), and brine (2 mL). The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (dichloromethane/ethyl acetate 70/30) to provide methyl 2-(tert-butoxy)-2-[4-(3,4-dihydro-2H-1-benzopyran-6-yl)-1-methyl-3-(3-oxocyclohex-1-en-1-yl)-1H-pyrazol-5-yl]acetate (43c) (63 mg, 0.139 mmol, 61%).

Provenance & Evidence