Ethyl 4-iodobenzoate → Ethyl 4-(3,3-dimethylcyclobutanecarbonyl)benzoate

Participants

Reaction Conditions

Reaction Steps

Ethyl 4-iodobenzoate (600 mg, 2.17 mmol) was dissolved in tetrahydrofuran (6.0 mL) and brought to −40° C. Isopropylmagnesium chloride lithium chloride complex solution (1.0 M in tetrahydrofuran, 0.365 mL, 2.17 mmol) was added dropwise and the yellow-red solution was stirred at −40° C. for 40 min. Cul (124 mg, 0.65 mmol) was added in one portion and the mixture was then stirred at −15° C. for 20 min to dissolve all the solids. The yellow solution was then brought back to −40° C. and 3,3-dimethylcyclobutanecarbonyl chloride (Intermediate 22) (450 mg, 3.07 mmol) was added dropwise. The color changed from slightly green to yellow, then red, then yellow. The mixture was warmed to 0° C. over 2 h in the same bath. The mixture was diluted with 1 N HCl and extracted with ethyl acetate (3 times). The combined organic layers were washed with brine, dried over Na2SO4, and concentrated in vacuo. The crude material was partially purified by silica gel flash chromatography (ethyl acetate/heptane) to give impure 4-(3,3-dimethyl-cyclobutanecarbonyl)-benzoic acid ethyl ester (588 mg). 1H NMR (400 MHz, CDCl3) δ 8.11 (d, J=8.4 Hz, 2H) 7.94 (d, J=8.4 Hz, 2H) 4.38-4.48 (m, 2H) 3.90 (quin, J=8.8 Hz, 1H) 2.16-2.29 (m, 2H) 2.04-2.13 (m, 2H) 1.42 (t, J=7.2 Hz, 3H) 1.28 (s, 3H) 1.09 (s, 3H); MS (M+1): 261.4.

Provenance & Evidence