Carbon Dioxide → 2-Fluoro-5-iodobenzoic acid

Participants

Reaction Steps

To a −78° C. solution of iPr2NH (16.80 mL, 0.12 mol) in 200 mL freshly distilled THF is added n-butyllithium (68 mL, 0.11 mol) dropwise, maintaining the temperature of the reaction below −65° C. The reaction is stirred for 10 minutes, then 1-fluoro-4-iodobenzene (11.50 mL, 0.10 mol) as a solution in 10 mL THF is added over 20 minutes. The reaction is stirred at −78° C. for 90 minutes, then cannulated rapidly into diethyl ether (180 mnL) and dry ice (approximately 75 g). The reaction is stirred at room temperature overnight. To the ether solution is added 1N NaOH (100 mL) and water (200 mL) and the solution placed in a separatory funnel. The aqueous layer is removed. The organic layer is washed with H2O (2×100 mL). All the aqueous portions are combined, chilled in ice/H2O, and acidified to pH 2 with 6N HCl. This solution is then extracted with diethyl ether (2×200 mL). The ether portions are combined, dried over Na2SO4, filtered, and concentrated to give a pale yellow solid. The solid is dissolved in a minimal amount of EtOAc on the steam bath, and hexanes are added to affect recrystallization. After standing in the freezer overnight, the product is obtained as a crystalline white solid (15.44 g, 0.058 mol, 58%). Physical characteristics are as follows: m.p. 157-159° C.; 1H NMR (300 MHz, CDCl3) δ 8.34, 7.88, 6.97; IR (drift) 3098, 3079, 3051, 3017, 3007, 2998, 2981, 2971, 2881, 2817, 1708, 1681, 1300, 1236, 824 cm−1; Anal. Calcd for C7H4FIO2: C, 31.61; H, 1.52; Found: C, 31.70; H, 1.59.

Provenance & Evidence