3-[[(1,1-Dimethylethoxy)carbonyl]amino]-L-alanine methyl ester

Chemical Properties

Viscous Yellow Oil

Uses

Methyl 3-[t-Butyloxycarbonyl)amino]-L-alanine (cas# 77087-60-6) is a compound useful in organic synthesis.

Synthesis

General procedure for the synthesis of methyl (S)-2-amino-3-((tert-butoxycarbonyl)amino)propionate from di-tert-butyl dicarbonate and methyl 2,3-diaminopropionate dihydrochloride: 10.0 g (0.053 mol) of methyl 2,3-diaminopropionate dihydrochloride was suspended in 1 L of dichloromethane, and cooled to -78 °C under argon protection. To this cold suspension triethylamine (30 ml, 0.20 mol) was added slowly and dropwise to obtain a clarified solution. Di-tert-butyl dicarbonate (11.6 g, 0.054 mol) was dissolved in 100 mL of dichloromethane and added dropwise to the above mixture. After dropwise addition, the reaction mixture was transferred to an ice bath and stirring was continued for 2 hours. After completion of the reaction, the mixture was transferred to a partition funnel and extracted with 2 x 50 mL of 10% Na2SO4 solution. The aqueous layer was washed with 3 x 10 mL dichloromethane and then the pH was adjusted to 10 with saturated NaHCO3 solution and 3N NaOH solution and extracted with 10 x 100 mL dichloromethane. The organic layers were combined, dried with anhydrous MgSO4, filtered and concentrated to give 4.9 g of light yellow oil. Purification by silica gel column chromatography with 2.5% methanol/ethyl acetate as eluent gave 4.32 g of the target product in 53% yield. High resolution mass spectrometry (HRMS): m/z 219.1324 (M + H+), 241.11436 (M + Na+). 1H NMR (300 MHz, CDCl3): δ [ppm] = 5.11 (s, 1H), 3.78-3.69 (s, 3H), 3.60-3.46 (m, 2H), 3.31-3.15 (m, 1H), 1.64 (m, 2H), 3.31-3.15 (m, 1H). 1H), 1.64 (s, 2H), 1.42 (s, 9H). 13C NMR (75 MHz, CDCl3): δ [ppm] = 174.46, 155.94, 79.48, 54.36, 52.26, 44.16, 28.30.

References

[1] Patent: WO2014/122228, 2014, A1. Location in patent: Page/Page column 23; 24
[2] Journal of Medicinal Chemistry, 2014, vol. 57, # 23, p. 9971 - 9982