Tetrahydrofuran → 5-cyanothiophene-2-carboxylic acid

Participants

Reaction Steps

In a 500 mL receiving flask are placed thiophene-2-carbonitrile (5.0 mL, 53.8 mmol) and THF (270 mL) and cooled in an acetone/solid CO2 bath. Lithium disopropylaoide (40.3 mL, 80.7 mmol, 2.0M solution in heptane/THF/ethylbenzene) is added in a slow stream via syringe. The solution is stirred for 10 min then quenched with an excess of dry ice. The reaction mixture is warned in a water bath and the THF removed in vacuo. The slurry is taken up in 1N NaOH and extracted with ether (3×). The aqueous layer is then acidified to pH<6 with conc. HCl, whereupon a brown precipitate forms. This precipitate is filtered off and to the resulting eluent is added 1N HCl which results in precipitation of the product. The product is collected by filtration then triturated with CH2Cl2Purification over silica gel (1:2.5:100 formic acid:MeOH:CH2Cl2) provides the product as a solid (1.79 g, 22%). 1H NMR (400 MHz, CDCl3) δ 14.10, 8.00, 7.80.

Provenance & Evidence