Methyl acetimidate hydrochloride

Chemical Properties

White to yellow powder

Uses

Methyl acetimidate hydrochloride has been used in pre-crystallization chemical modification of lysine residues.

General Description

Methyl acetimidate hydrochloride is an inhibitor of N-methylation of phosphatidylethanolamine. It also prevents the stimulation of purified cardiac sarcolemmal vesicles Ca²⁺-pump activities.

Synthesis

1) Example 1-1: Preparation of methyl acetimidate hydrochloride 1.6 kg of acetonitrile and 2.4 kg of methanol were added to the reactor and the reaction system was cooled to -10 °C. 3.67 kg of acetyl chloride was slowly added dropwise with stirring, and the rate of dropwise acceleration was controlled to maintain the reaction temperature at 0 °C. After the dropwise addition, the reaction mixture was continued to be stirred at room temperature for 12 hours. After completion of the reaction, the volatile solvent was removed by distillation under reduced pressure at 45 °C. To the residue was added 11.8 kg of tert-butyl methyl ether and stirred at room temperature for 3 hours to promote crystallization. The precipitated solid product was collected by filtration and dried under vacuum at 40 °C to give 4.1 kg of methylglyoxylate hydrochloride (yield: 95%). The product was characterized by 1H-NMR (400 MHz, DMSO-d6): δ 11.7 (s, 2H), 4.07 (s, 3H), 2.38 (s, 3H).

Purification Methods

Crystallise the imidate from methanol by adding dry ether to a ratio of 1:1 and cooling at 0o. Filter off the crystals in a cold room, wash them with methanol/ether (1:2), then dry in a vacuum. [Hunter & Ludwig J Am Chem Soc 84 3491 1962.] The free base has b 90-91o/765mm, d 0.867, n 1.403. [Hunter & Ludwig Methods Enzymol 25 585 1973, Beilstein 2 IV 181.]

References

[1] Journal of Organic Chemistry, 1986, vol. 51, # 26, p. 5111 - 5123
[2] Patent: WO2015/5615, 2015, A1. Location in patent: Paragraph 138; 139; 140
[3] Chemische Berichte, 1985, vol. 118, # 8, p. 3089 - 3104
[4] Analytical Chemistry, 2006, vol. 78, # 18, p. 6398 - 6403
[5] Synlett, 2001, # 11, p. 1707 - 1710