Boc-Phe-n(OCH3)CH3

Chemical Properties

Light Yellow Oil

Uses

An intermediate for the synthesis of some HIV protease inhibitors.

Uses

Reduced by LiAlH4 to give the corresponding Boc amino acid aldehyde.

Synthesis

GENERAL PROCEDURE: Methoxymethylamine (0.360 g, 6.0 mmol) and BOC-L-phenylalanine (0.244 g, 2.0 mmol) were dissolved in anhydrous toluene (10 mL) and stirred for 10 min at 0 °C. Subsequently, a solution of phosphorus trichloride (0.137 g, 1.0 mmol) in anhydrous toluene (2 mL) was slowly added dropwise to the reaction mixture. The reaction system was gradually warmed up to room temperature and then stirred for 0.5 h at 60 °C. The reaction process was monitored by thin layer chromatography (TLC). Upon completion of the reaction, the mixture was cooled to room temperature, quenched with saturated sodium bicarbonate solution (20 mL) and extracted with ethyl acetate (3 x 10 mL). The organic phases were combined and dried with anhydrous magnesium sulfate. The solvent was removed by concentration under reduced pressure and the resulting crude product was purified by column chromatography (silica gel, petroleum ether-ethyl acetate, 3:2) to afford the target compound (S)-(tert-butyl (S)-(1-(methoxy(methyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate as a colorless oil in 320 mg (97%) yield.

References

[1] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 12, p. 3229 - 3232
[2] Journal of Medicinal Chemistry, 1992, vol. 35, # 4, p. 641 - 662
[3] Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 20, p. 2855 - 2858
[4] Heteroatom Chemistry, 2003, vol. 14, # 7, p. 603 - 606
[5] Journal of Medicinal Chemistry, 2013, vol. 56, # 23, p. 9556 - 9568