2-Methoxyethoxymethyl chloride explained

2-Methoxyethoxymethyl chloride is an organic compound with formula . A colorless liquid, it is classified as a chloroalkyl ether. It is used as an alkylating agent. In organic synthesis, it is used for introducing the methoxyethoxy ether (MEM) protecting group.^[1] MEM protecting groups are generally preferred to methoxymethyl (MOM) protecting groups, both in terms of formation and removal.

Typically, the alcohol to be protected is deprotonated with a non-nucleophilic base such as N,N-diisopropylethylamine (DIPEA) in dichloromethane followed by addition of 2-methoxyethoxymethyl chloride.^{[2] [3]}

The MEM protecting group can be cleaved (deprotection) with a range of Lewis and Bronsted acids.^[4]

Safety

The closely related chloromethyl methyl ether is a known human carcinogen.^[5]

References

1. Book: 10.1002/047084289X.rm100 . 2-Methoxyethoxymethyl Chloride . Encyclopedia of Reagents for Organic Synthesis . 2001 . Wuts . Peter G. M. . 0471936235 .
2. Corey. E. J.. Gras. Jean-Louis. Ulrich. Peter. 1976-03-01. A new general method for protection of the hydroxyl function. Tetrahedron Letters. 17. 11. 809–812. 10.1016/S0040-4039(00)92890-9.
3. Lee. Hong Myung. Nieto-Oberhuber. Cristina. Shair. Matthew D.. 2008-12-17. Enantioselective Synthesis of (+)-Cortistatin A, a Potent and Selective Inhibitor of Endothelial Cell Proliferation. Journal of the American Chemical Society. 130. 50. 16864–16866. 10.1021/ja8071918. 0002-7863. 19053422. 207132632 .
4. Amano. Seiji. Takemura. Noriaki. Ohtsuka. Masami. Ogawa. Seiichiro. Chida. Noritaka. 1999-03-26. Total synthesis of paniculide A from d-glucose. Tetrahedron. 55. 13. 3855–3870. 10.1016/S0040-4020(99)00096-4.
5. bis(Chloromethyl) Ether and Technical-Grade Chloromethyl Methyl Ether CAS Nos. 542-88-1 and 107-30-2 Report on carcinogens, eleventh edition