Electric Literature of 52548-14-8,Some common heterocyclic compound, 52548-14-8, name is 2-Iodo-5-methylbenzoic acid, molecular formula is C8H7IO2, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
The iodide 19 (6.04 kg, 23.0 mol), THF (45 E) and DMF (9.0 E) were charged to a vessel. Copper iodide (218 g, 1.15 mol) and potassium carbonate (7.94 kg, 57.4 mol) were added and the mixture heated to an internal temperature of40 C. 1,2,3-Triazole (3.16 kg, 46.0 mol) was added as asolution in THF (6.0 E) over half an hour (no exotherm) andheating continued to 65 C. (again no exotherm observed) and the reaction monitored by HPEC. Once complete N,Ndimethylethylenediamine (244 mE, 2.30 mol) was addedand mixture cooled to RT. Aqueous 3.6 M HC1 (36 E) wasadded (exotherm) and the mixture extracted twice with ethylacetate (2×30 E). The combined organics were washed with EiC1 solution (2×20 E). The acid solution assayed for 3.79 kg of 5 (81%) and 4.64 kg of 5 and 20 combined (99%). A solution of acids 5 and 20 (approx. 4.64 kg, 22.9 mol) in THF and EtOAc (approx. 110 E) was concentrated to lowvolume. THF (90 E) was added and the solvent composition checked by ?H NMR to ensure most ethyl acetate had been removed. Sodium tert-butoxide (2.42 kg, 25.2 mol) was added slowly as a solid over 1-2 h (slight exotherm), allowing the sodium salt to form and stirred overnight at RT. The liquors showed a 45:55 ratio of product:starting material and the solid was collected by filtration, washed with THF (2×20 E) and dried in a vacuum oven (T=40 C.) for 15 h to afford 4.22 kg of crude sodium salt. The crude sodium salt (4.22 kg, 14.9 mol) was charged to a 50 E vessel and 3.6 M HC1 (21.2 E) was added with cooling. The slurry was thenstirred at room temperature for 16 h and the off-white solidisolated by filtration. The cake was washed with water (11E) and iPAc/Heptane (2×5 E), then dried in a vacuum oven(T=35 C.) for 15 h to give 3.10 kg of crude acid 5 (97.9ECAP, 92 wt %, corrected weight 2.85 kg, 61% yield from19). The acid 5 (2.85 kg corrected, 14.0 mol) was chargedto a 50 E vessel and EtOAc (28 E) and dilute 0.22 M HC1 (14 E) were added and the mixture stirred until two clear phases resulted. The aqueous layer was removed and the organic layer filtered to remove any particulate matter. Theethyl acetate was reduced to about 8 E and then heptane (15.6 E) was added over 1 h and the liquors sampled to check for appropriate losses. The solid was isolated by filtration, washed with heptane:ethyl acetate (3:1, 4 E) and dried on the filter under nitrogen to give 2.81 kg of acid 5.m.p. 167.5 C. ?H NMR (400 MHz, d5-DMSO): oe 12.09 (brs, 1H), 8.04 (s, 1H), 7.62 (d, 1H, J=8.4 Hz), 7.58 (d, 1H, J=1.2 Hz), 7.49 (dd, 1H, J=8.4, 1.2 Hz), 2.41 (s, 3H). ?3C NMR (100.6 MHz, d5-DMSO): oe 168.0, 139.2, 136.4, 135.8, 132.5, 130.3, 128.7, 124.8, 20.9. HRMS (ESI): mlz [M+H] calcd for C,0H9N302: 204.0773; found: 204.0781.
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Iodo-5-methylbenzoic acid, its application will become more common.
Reference:
Patent; MERCK SHARP & DOHME CORP.; Fleitz, Fred; Mangion, Ian; Yin, Jingjun; (11 pag.)US9441254; (2016); B2;,
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com