Benzo(B)Thiophene → HCID 86755300, compound

Participants

Reaction Conditions

Reaction Steps

n-Butyllithium (25 ml of 1.6N solution in hexanes) was added dropwise to a stirred solution of benzothiophene (5.36 g, Lancaster) in tetrahydrofuran (80 ml) under argon and cooled to -78° C. When the addition was complete the reaction was stirred at -78° C. for 10 min and then at room temperature for 20 min. The solution was then added via a cannula to a stirred solution of diethyl oxalate (11.68 g), cooled to -78° C. The mixture was stirred at -78° C. for 0.5 h and then at room temperature for 1 h. Acetic acid (1.5 ml) was added to the mixture which was then partitioned between ethyl acetate and water. The organic phase was washed three times with water, then with sodium bicarbonate solution, water and brine. The solution was dried over magnesium sulphate and evaporated. Column chromatography using gradient elution (Kieselgel:9:1 to 4:1 hexane:ethyl acetate) gave a mixture of ethyl-2-oxo-2-(2-benzothienyl)acetate and diethyl oxalate. The mixture was dissolved in ethanol (50 ml) and hydroxylamine hydrochloride (435 mg) was added. The mixture was stirred at room temperature for 3 days, then the solvent was evaporated and the residue partitioned between ethyl acetate and water. The organic phase was washed with water and brine, dried over magnesium sulphate and evaporated. The isomers of the title oxime were separated by column chromatography of the residue (Kieselgel:4:1 hexane:ethyl acetate). Isomer A: 887 mg, νmax (CHCl3)/cm-1 3564, 3309 and 1736. δH (250 MHz; CDCl3), 1.46 (3H, t, J 7.08), 4.53 (2H, q, J 7.11), 7.31-7.42 (2H, m), 7.46 (1H, s), 7.72-7.82 (2H, m), 8.83 (1H, s); m/z (EI) 249 (M+). Isomer B: 624 mg, νmax (CHCl3)/cm-1 3545, 3249, 1731. δH (250 MHz; CDCl3), 1.49 (3H, t, J 7.19), 4.49 (2H, q, J 7.25), 7.35-7.47 (2H, m), 7.86-7.93 (2H, m), 8.40 (1H, s), 10.43 (1H, br.s); m/z (EI) 249 (M+).

Provenance & Evidence