Acetic Acid → N-(2-Boc-amino-ethyl)alanine benzyl ester

Participants

Reaction Conditions

Reaction Steps

Alanine benzyl ester (10, 8.82 g, 49 mmol, 1 eq) was dissolved in MeOH (100 ml) and glacial acetic acid (10.34 g, 172 mmol, 3.5 eq) was added. The mixture was stirred at 0° C. under nitrogen and sodium cyanoborohydride (10.82 g, 172 mmol, 3.5 eq) was added. Boc-aminoacetaldehyde (15.67 g, 98 mmol, 2 eq) in MeOH (200 ml) was added dropwise during 2h. The reaction mixture was stirred at 0° C. for 35 min. and then at 4°-5° C. overnight. Water (300 ml) was added to the reaction mixture and the pH was adjusted to 9 by addition of solid sodium carbonate. The saturated solution was filtered and subsequently extracted with ether (3×500 ml). The organic phase was washed with a 1:1 mixture of saturated aqueous solutions of sodium chloride and sodium bicarbonate (1×450 ml), dried (Na2SO4), filtered and evaporated under reduced pressure to give 22.60 g of crude N-(2-Boc-amino-ethyl)alanine benzyl ester as a slightly golden oil. The crude product was dissolved in dry ether (500 ml) and stirred at 0° C. HCl in ether (60 ml) was then added to the solution, and the resulting precipitate was collected by filtration and washed with cold dry ether (3×20 ml) affording 7.21 g (41%) of 11 as white crystals. A second crop of 2.12 g (12%) could be collected as a white semicrystalline material by keeping the mother liquor in the freezer overnight. This second crop was slightly less pure than the first crop. 1H-NMR (D2O/TMS): δ1.36 (s, 9H, Boc); 1.52 (d, J=7.2 Hz, 3H, Me); 3.16 (m, 2H, NCH2); 3.35 (m, 2H, NCH2); 4.17 (q, J=7.2 Hz, 1H, CH); 5.26 (s, 2H, CH2Ph); 7.40 (s, 5H, Ph). 13C-NMR (D2O/TMS): δ13.5 (Me); 27.3 (Box); 36.4 (CH); 45.5 (NCH2); 55.2 (NCH2); 68.4 (CH2Ph); 128.3, 128.7, 128.8 (Ph). MS(FAB+) m/z (%): 323 (100, M-HCl+H) Anal. Calcd for C17H27CIN2O4 : C, 56.90; H, 7.58; N, 7.81; Cl, 9.88. Found: C, 55.11; H, 7.52; N, 7.93; Cl, 10.45.

Provenance & Evidence