Uses
N-Boc-p-nitro-L-phenylalanine is the N-Boc protected form of p-Nitro-L-phenylalanine (N502725, Hydrate) and is a useful synthetic intermediate in the synthesis of Hydroxymelphalan (H939850); an analog of Melphalan (M216900) which is an antineoplastic.
Synthesis
To a stirred solution of 4.0 g of (S)-2-amino-3-(4-nitrophenyl)propanoic acid (0.019 mol) in 30 cm3 tert-butanol and 0.8 g of NaOH (0.0209 mol, dissolved in 5 cm3 of water) was added slowly and dropwise at 0 °C 5 cm3 of di-tert-butyl dicarbonate (0.0228 mol, dissolved in 5 cm3 of tert-butanol). The reaction mixture was stirred for 10 h at room temperature. After completion of the reaction (confirmed by thin layer chromatography), the solvent was removed by evaporation and the residue was poured into water and extracted with ethyl acetate (2 x 50 cm3). The organic phases were combined, washed sequentially with 50 cm3 10% citric acid solution and 50 cm3 saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give (S)-2-((tert-butoxycarbonyl)amino)-3-(4-nitrophenyl)propionic acid as a white solid. Yield: 5.0 g (86% yield); Melting point: 105-106°C (literature value 105-107°C).
References
[1] Journal of Organic Chemistry, 1996, vol. 61, # 5, p. 1872 - 1874
[2] Journal of Organic Chemistry, 1999, vol. 64, # 10, p. 3467 - 3475
[3] Patent: US2002/35137, 2002, A1
[4] Monatshefte fur Chemie, 2016, vol. 147, # 11, p. 2001 - 2008
[5] Journal of Medicinal Chemistry, 1989, vol. 32, # 3, p. 638 - 643
