Methyl chloroformate → HCID 90093357, compound

Participants

Reaction Conditions

Reaction Steps

A solution of ethyl 2-(3-bromo-4-iodo-1-methyl-1H-pyrazol-5-yl)-2-oxoacetate (11f) (750 mg, 1.94 mmol), potassium carbonate (536 mg, 3.88 mmol), and 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)chroman (494 mg, 1.90 mmol) in a mixture of dioxane (16 mL) and water (4 mL) was degassed for 5 minutes. Palladium tetrakis(triphenylphosphine) (157 mg, 0.14 mmol) was added and the reaction mixture was heated at 120° C. overnight. After concentrating in vacuo, the residue was dissolved in 1N sodium hydroxide (15 mL). The aqueous layer was washed with diethyl ether (20 mL), acidified with 1M hydrochloric acid until pH 3 and extracted with diethyl ether (2×15 mL). The organic layer was dried over sodium sulfate and concentrated in vacuo. The crude was dissolved in dichloromethane (7 mL), cooled to 0° C., and under a nitrogen atmosphere, triethylamine (0.41 mL, 2.91 mmol) and methyl chloroformate (0.22 mL, 2.91 mmol) were added. The reaction mixture was stirred at 0° C. for 30 minutes, and allowed to reach room temperature. Dichloromethane (10 mL) was added, and the mixture was successively washed with 1N hydrochloric acid (10 mL), a saturated solution of sodium hydrogenocarbonate (10 mL), and brine (10 mL). The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (cyclohexane/ethyl acetate 90/10) to provide methyl 2-[3-bromo-4-(3,4-dihydro-2H-1-benzopyran-6-yl)-1-methyl-1H-pyrazol-5-yl]-2-oxoacetate (11g) (531 mg, 1.40 mmol, 72%) as a yellow solid.

Provenance & Evidence