2(3H)-Benzofuranone → HCID 14143242, compound

Participants

Reaction Conditions

Reaction Steps

A 2000-mL 3-neck flask fitted with nitrogen inlet, low temperature thermometer, and 500-mL pressure equilibrated dropping funnel is flame dried and charged with dry hexane (freshly distilled from calcium hydride, 200 mL). The flask is cooled with an external dry ice/acetone bath then tert-butyl-lithium (1.7 M in pentane, 200 mL, 340 mmol) is added via double ended needle transfer. The resulting solution is cooled to -65° C. internal temperature then a solution of 43 (40.00 g, 294 mmol) in a mixture of ether (100 mL) and hexane (300 mL) is added dropwise over 1 hour at a rate such that the reaction temperature does not exceed -55° C. Upon completion of the addition the reaction mixture is stirred with dry ice/acetone cooling for 10 minutes, the cooling bath is removed and the reaction allowed to gradually warm. After 1 hour the temperature reaches about 5° C. The reaction is quenched by dropwise addition of water (40 mL), followed immediately by 2N HCl (200 mL) and tetrahydrofuran (200 mL). The reaction mixture is then poured into a 4000-mL Erlenmeyer flask containing 2N HCl (200 mL) and the resulting mixture diluted to a total volume of 2800 mL with tetrahydrofuran. The elimination is allowed to proceed for 2.5 hours then 20% NaCl (500 mL) was added and the layers separated. The aqueous layer was reextracted with ether (500 mL) and the combined organic layers washed with 20% NaCl (500 mL), dried (Na2SO4) and concentrated to a reddish oil (48.7 g) which is distilled. The total distillate is chromatographed (Water Prep 500A) using hexane as eluant to afford 4-tert-butyl-6,7-dihydrobenzofuran as a colorless liquid.

Provenance & Evidence