Uses
tert-Butyl 1-Methylhydrazinecarboxylate is a reactant in the synthesis of the hydrazide of (2S,3S)-trans-epoxysuccinyl-L-leucylamido-3-methylbutane, the lead structure of the irreversible cathepsin C inhibitor.
Synthesis
Methylhydrazine (7) (26 g, 564 mmol) and sodium hydroxide (23 g, 575 mmol) were dissolved in methanol (500 mL). A solution of di-tert-butyl dicarbonate (123 g, 564 mmol) in methanol (500 mL) was added slowly and dropwise to this solution over a period of 2 h at 0°C. The reaction mixture was stirred at room temperature. The reaction mixture was stirred at room temperature for 2 h. The insoluble material was removed by filtration through diatomaceous earth. The filtrate was concentrated under reduced pressure and the oily residue obtained was neutralized with aqueous ammonium chloride. Subsequently, the aqueous phase was extracted with dichloromethane, the organic phase was dried with anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure to afford 1-tert-butoxycarbonyl-1-methylhydrazine (8) (79 g, 97% yield). The product was characterized by 1H NMR (CDCl3): δ 4.06 (br, 2H), 3.05 (s, 3H), 1.47 (s, 9H); IR (pure) νmax 1694, 1365, 1154 cm-1.
References
[1] Bioorganic and Medicinal Chemistry Letters, 2003, vol. 13, # 14, p. 2413 - 2418
[2] Chirality, 2013, vol. 25, # 6, p. 341 - 349
[3] Journal of Antibiotics, 1993, vol. 46, # 8, p. 1279 - 1288
[4] Patent: US5275816, 1994, A
[5] Bioorganic Chemistry, 2010, vol. 38, # 5, p. 229 - 233
