84000-01-1

103478-58-6

The general procedure for the synthesis of (R)-2-((((9H-fluoren-9-yl)methoxy)carbonyl(methyl)amino)-3-methylbutanoic acid from (S)-3-Fmoc-4-isopropyl-5-oxoxoxazolidine was as follows: the Fmoc-valyl oxazolidinone (2.80 g, 8.00 mmol) was dissolved in chloroform (40 mL). To this solution, trifluoroacetic acid (1.85 mL, 24.0 eq.) and triethylsilane (3.83 mL, 24.0 eq.) 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 partitioned between ether and 5% sodium bicarbonate solution. The aqueous phases were combined and the pH was adjusted to 2 with 5 M hydrochloric acid, followed by extraction with ethyl acetate. The organic phases were combined, dried with anhydrous magnesium sulfate, and concentrated to give Fmoc-N-methylvaline (4) as a white solid (2.35 g, 83% yield).Fmoc-N-methylvaline was recrystallized by ethyl acetate to give white acicular crystals: melting point 186-187 °C (literature value 33: 185-187 °C); low resolution mass spectra (ESI) m/z [M + H ]+ 354.1 (100%), [M + Na]+ 376.1 (61%); IR spectrum (NaCl) νmax (cm-1) 3420 (broad, OH), 2964 (aliphatic CH), 1700 (C=O), 1445, 1305 (C=C); 1H NMR (300 MHz, CDCl3) δH (ppm) 7.63 (2H, d, J=7.5 Hz, ArH), 7.46 (2H, d, J=6.9 Hz, ArH), 7.26 (2H, t, J=7.2 Hz, ArH), 7.17 (2H, t, J=7.5 Hz, ArH), 4.28 (2H, m, CHCH2O), 4.22 (1H, m, (Ar)2CHCH2). 4.13 (1H, m, NCHCO), 2.79 (3H, d, J=4.2 Hz, NCH3), 2.02 (1H, m, CH3CHCH3), 0.88 (3H, dd, J=6.6, 19.2 Hz, CH3CHCH3), 0.72 (3H, dd, J=6.6, 13.8 Hz, CH3CHCH3) ( IR and 1H NMR data are consistent with literature reports); 13C NMR (75 MHz, CDCl3) δC (ppm) 175.5, 159.6, 146.6, 143.9, 130.4, 129.7, 127.7, 122.6, 70.3, 66.9, 49.9, 33.1, 30.2, 22.5, 21.7.