Chlorotrimethylsilane → Ethyl 3-(2-fluoro-5-iodophenyl)-3-oxopropanoate

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-fluoro-5-iodobenzoic acid (4.03 g, 15.14 mmol) in 11 mL freshly distilled THF is added CDl (2.96 g, 18.24 mmol) in small portions. Vigorous gas evolution is observed. The reaction is stirred overnight. In a separate flask, ethyl malonate potassium salt (2.84 g, 16.69 mmol) is suspended in 10 mL CH3CN. To this solution is added chlorotrimethylsilane (2.15 mL, 16.94 mmol) and the reaction is stirred at room temperature overnight. The latter reaction is cooled to 0° C. and DBU (5.00 mL, 33.43 mmol) is added dropwise. This reaction is stirred at 0° C. for 3 h. The solution of the CDI adduct is then cannulated over and the mixture is stirred at 0° C. for 2 h. Upon complete conversion to product as evidenced by TLC, the solution is quenched with water and 6N HCl (8 mL). The reaction is partitioned with diethyl ether. The organic layer is washed with 1N HCl and then brine, dried over Na2SO4, filtered, and concentrated to give a light orange oil. The oil is dissolved in EtOAc and adsorbed onto silica. Purification by chromatography (eluent 3% EtOAc/hexanes) affords the desired product as a colorless oil which crystallized upon standing (2.51 g, 7.46 mmol, 49%). Physical characteristics are as follows: m.p. 54-56° C.; 1H NMR (300 MHz, CDCl3) δ 12.67, 8.18, 7.70, 6.89, 5.54, 4.28, 1.35; IR (drift) 2984, 1627, 1558, 1476, 1422, 1390, 1358, 1292, 1262, 1221, 1201, 1071, 1028, 823, 807 cm −1; MS (EI) m/z 336 (M+), 336, 249, 122, 107, 94, 86, 84, 69, 68, 51; Anal. Calcd for C11H10FIO3: C, 39.31; H, 3.00; Found: C, 39.35; H, 2.92.

Provenance & Evidence