Sodium Chloride → 5-Methoxy-6-methyl-1H-indene-3-carbonitrile

Participants

Reaction Conditions

Reaction Steps

A solution of 10.7 grams (0.061 mole) of 6-methoxy-5-methylindan-1-one (ii), 29.7 grams (0.182 mole) of diethyl cyanophosphonate, and 6.1 grams (0.182 mole) of lithium cyanide in 250 mL of anhydrous THF was stirred at ambient temperature for five hours. GC analysis of the reaction mixture indicated that the reaction was not complete. The reaction mixture was warmed to 45° C., where it was stirred for about 16 hours. After this time, an aliquot of the reaction mixture was placed water and the mixture was extracted with ethyl acetate. GC analysis of the extract indicated that the reaction was about 10% complete. An additional 0.182 mole each of diethyl cyanophosphonate and lithium cyanide were added to the reaction mixture, and heating at 45° C. was continued for about an additional eight hours. After this time, the reaction mixture was poured into about 300 mL of an aqueous solution saturated with sodium chloride, and then it was extracted with two 300 mL portions of ethyl acetate. The combined extracts were then washed with three portions of an aqueous solution saturated with sodium chloride and dried with sodium sulfate. The mixture was filtered and the filtrate was concentrated under reduced pressure to a residue. The residue was dissolved in toluene and again concentrated under reduced pressure to a residue. The residue was taken up in 500 mL of toluene and 20.7 grams (0.182 mole) of boron trifluoride diethyl etherate was added. Upon completion of addition, the reaction mixture was stirred at ambient temperature for about six hours. The reaction mixture was treated as set forth above, yielding a residue. The residue was purified by column chromatography on silica gel using mixtures of hexane and diethyl ether as an eluant. The appropriate fractions of eluate were combined and concentrated under reduced pressure, yielding 2.8 grams of subject compound. The NMR spectrum was consistent with the proposed structure.

Provenance & Evidence