Synlett, Table of Contents Synlett 2018; 29(11): 1451-1554DOI: 10.1055/s-0037-1610132 letter © Georg Thieme Verlag Stuttgart · New York Pharmaceutical-Oriented Methoxylation of Aryl C(sp2)–H Bonds using Copper Catalysts Guofu Zhang a College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014, P. R. of China Email: dingcr@zjut.edu.cn , Jianfei Zhu a College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014, P. R. of China Email: dingcr@zjut.edu.cn , Chaolai Tong b Jianxing Honor College, Zhejiang University of Technology, Hangzhou 310014, P. R. of China , Chengrong Ding* a College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014, P. R. of China Email: dingcr@zjut.edu.cn › Author Affiliations Recommend Article Abstract Buy Article All articles of this category Abstract A pharmaceutical-oriented, copper(II)-catalyzed methoxylation of aryl C(sp2)–H bonds has been developed. This simple and environmentally benign reaction system occurs efficiently using oxygen as oxidant with broad substrate scope and high functional group tolerance. Key words Key wordspharmaceutical development - C–H methoxylation - copper catalysis - oxygen - DMEDA Full Text References References and Notes 1a Ohkawa S. Fukatsu K. Miki S. Hashimoto T. Sakamoto J. Doi T. Nagai Y. Aono T. J. Med. Chem. 1997; 40: 559 1b Esteki M. Khayamian T. Chem. Biol. Drug Des. 2008; 72: 409 1c Kubo K. Kohara Y. Imamiya E. Sugiura Y. Inada Y. Furukawa Y. Nishikawa K. Naka T. J. Med. Chem. 1993; 36: 2182 2a Hartwig JF. Nature 2008; 455: 314 2b Ley SV. Thomas AW. Angew. Chem. Int. Ed. 2003; 42: 5400 2c Liu B. Shi B.-F. Tetrahedron Lett. 2015; 56: 15 2d Krylov IB. Vil’ VA. Terent’ev AO. Beilstein J. Org. Chem. 2015; 11: 92 2e Monnier F. Taillefer M. Angew. Chem. Int. Ed. 2009; 48: 6954 2f Qiao JX. Lam PY. S. Synthesis 2011; 829 2g Ma D. Cai Q. Org. Lett. 2003; 5: 3799 2h Cai Q. Zou B. Ma D. Angew. Chem. 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After cooling to room temperature, the solvent was evaporated under vacuum. The residue was dissolved in mixed solvent of dichloromethane (30 mL) and edetate tetrasodium (EDTA) saturated aqueous solution (30 mL). After separation, the aqueous phase was extracted twice with dichloromethane (15 mL) and the organic layers were combined and evaporated under vacuum. The crude product was purified by column chromatography using silica gel to afford 4-bromo-N-(2-(dimethylamino)ethyl)-2-methoxybenzamide. Isolated yield: 0.0542 g (90%). 1H NMR (500 MHz, CDCl3): δ = 8.33 (s, 1 H), 8.01 (d, J = 8.4 Hz, 1 H), 6.97 (dd, J = 8.4, 1.8 Hz, 1 H), 6.89 (d, J = 1.8 Hz, 1 H), 3.92 (s, 3 H), 3.66 (q, J = 5.9 Hz, 2 H), 2.87–2.80 (m, 2 H), 2.50 (s, 6 H). 13C NMR (126 MHz, CHCl3): δ = 164.84, 158.08, 138.54, 133.11, 121.34, 119.82, 112.04, 57.77, 56.29, 44.68, 36.56. HRMS (ESI): m/z [M]+ calcd for C12H18ClN2O2: 257.1051; found: 257.1062. Supplementary Material Supplementary Material Supporting Information
