Benzaldehyde → NepsilonBenzyl-Nalpha-BOC-L-Lysine tert-Butyl Ester

Participants

Reaction Steps

Nα-BOC-L-lysine t-butyl ester hydrochloride salt (3) (25.97 g, 76.64 mmol) was dissolved in CHCl3 (300 ml) and washed with saturated aqueous Na2CO3 solution (2×100 ml). The organic layer was separated, dried (MgSO4), filtered and concentrated. The resultant oil (the free amine) was combined with benzaldehyde (10.42 g, 98.13 mmol), EtOH (150 ml) and activated 3 Å molecular sieves (46.0 g). The mixture was stirred under N2 for 6 hours. Sodium cyanoborohydride (2.41 g, 38.4 mmol) was added, and the mixture was stirred overnight at room temperature. The brown mixture was filtered, and the filtrate was acidified to pH 2 with 1 N HCl (110 ml). The yellow solution was concentrated to dryness, dissolved in CHCl3, and washed with saturated Na2CO3 solution and water. The organic layer was separated, dried (MgSO4) and concentrated. Flash column chromatography (10% EtOH/CHCl3, Rf=0.30) afforded the Nε-benzyl-Nα-BOC-L-lysine t-butyl ester (4) (16.16 g, 54%) as a colorless oil. 1H NMR (CD3OD) δ 7.34-7.20 (m, 5H), 3.91 (dd, 1H, J=9.0, 5.1), 3.72 (s, 2H), 2.58 (t, 2H, J=7.2), 1.82-1.30 (m, 6H), 1.45 (s, 9H), 1.43 (s, 9H); 13C NMR (CDCl3) δ 171.9, 155.3, 140.1, 128.3, 128.1, 126.9, 81.6, 79.5, 53.9, 48.9, 32.7, 29.5, 28.3, 27.9, 22.9. HRMS m/z calcd. for C22H36N2O4 392.2675, found 392.2676. Anal. calcd. for C22H36N2O4: C 67.32, H 9.24, N 7.14. Found: C 67.40, H 9.28, N 7.16. [α]25D=6.9° (c =1.00, CHCl3).

Provenance & Evidence