Synthesis
General procedure for the synthesis of (tert-butoxycarbonyl)-L-leucine methyl ester from di-tert-butyl dicarbonate and L-leucine methyl ester hydrochloride: firstly, L-leucine methyl ester hydrochloride and K2CO3 were suspended in water and stirred for 1 hour to release the free amino acid ester. Subsequently, the free amino acid ester was extracted with CH2Cl2 and the organic phase was dried with MgSO4. Evaporation of CH2Cl2 under reduced pressure gave the free amino acid ester, which should be used immediately in the next step of the N-Boc protection reaction. Next, the free amino acid ester (1 mmol) was dissolved in 1 mL of ethanol and added to a solution of di-tert-butyl dicarbonate (1.2 mmol) and guanidine hydrochloride (15 mol%) in ethanol (1 mL) that had been preheated to 35-40 °C and the reaction was stirred at the appropriate temperature. After completion of the reaction, the post-treatment procedure was the same as that for conventional amines.
References
[1] Tetrahedron Letters, 2011, vol. 52, # 12, p. 1260 - 1264
[2] Chemistry - A European Journal, 2013, vol. 19, # 12, p. 3817 - 3821
[3] Journal of Organic Chemistry, 1995, vol. 60, # 24, p. 8074 - 8080
[4] Chemical Biology and Drug Design, 2012, vol. 79, # 2, p. 216 - 222
[5] European Journal of Medicinal Chemistry, 2017, vol. 135, p. 142 - 158
