Synthesis
Fmoc-phenylalanyl oxazolidinone (4.60 g, 11.6 mmol) was dissolved in chloroform (58 mL). To this solution, trifluoroacetic acid (2.68 mL, 34.8 equiv) and triethylsilane (5.56 mL, 34.8 equiv) were added sequentially. The reaction mixture was stirred at room temperature until the reaction was complete (24-72 hours). Upon completion of the reaction, the solution was concentrated and subsequently partitioned between ether and saturated sodium bicarbonate solution. The aqueous phase was combined, acidified to pH 2 with 5 M hydrochloric acid and extracted with ethyl acetate. The organic phase was collected, dried with anhydrous magnesium sulfate and concentrated to give a dark yellow oily product. The crude product was dissolved in dichloromethane and repeatedly evaporated to yield Fmoc-N-methylphenylalanine as a brown solid (3.73 g, 80% yield): melting point 106-107 °C; low-resolution mass spectrometry (ESI) m/z [M + H]+ 402.1 (100%); 1H NMR (300 MHz, CDCl3) δH (ppm) (rotated isomer ) 7.74 (2H, d, J = 7.5 Hz, ArH), 7.49 (1H, d, J = 7.8 Hz, ArH), 7.43 (1H, t, J = 6.9 Hz, ArH), 7.37 (2H, t, J = 7.5 Hz, ArH), 7.25-7.21 (6H, m, ArH), 6.95 (1H, d, J = 6.3 Hz , ArH), 4.89 (1H, dd, J = 5.1, 11.1 Hz, NCHCOOH), 4.59-4.53 (1H, m, (Ar)2CHCH2), 4.38 (2H, d, J = 14.4 Hz, CHCH2O), 3.41-3.35 (1H, m, CHCHHAr), 3.16-3.08 (1H m, CHCHHAr), 2.77 (3H, s, NCH3), 2.75 (3H, s, NCH3) (1H NMR data are consistent with literature reports); 13C NMR (75 MHz, CDCl3) δC (ppm) 175.5, 156.5, 143.4, 140.9, 136.4, 128.4, 128.3, 127.3, 126.7, 126.5, 124.6, 124.3, 119.6, 67.6, 60.7, 46.7, 34.3, 32.3.
References
[1] Journal of Organic Chemistry, 2005, vol. 70, # 17, p. 6918 - 6920
[2] European Journal of Organic Chemistry, 2013, # 21, p. 4509 - 4513
[3] Tetrahedron, 2014, vol. 70, # 14, p. 2351 - 2358
[4] Tetrahedron Letters, 2006, vol. 47, # 11, p. 1691 - 1694
[5] Angewandte Chemie - International Edition, 2008, vol. 47, # 14, p. 2595 - 2599
