4-Methylmorpholine → Leucinamide

Participants

Reaction Conditions

Reaction Steps

0.2 g (0.218 mmol) of N-[N-[N-[N-[N-[3-(tert-butoxycarbonyl)propionyl]-O-tert-butyl-L-α-aspartyl]-O-tert-butyl-L-α-glutamyl]-2-methyl-L-phenylalanyl]-3-methyl-L-valyl]-L-leucine was dissolved in 2 ml of dimethylformamide and 6 ml of dichloromethane. 0.12 ml (1.1 mmol) of N-methylmorpholine was added and the solution was cooled to -15° C. under a nitrogen atmosphere. 40 mg (0.31 mmol) of isobutyl chloroformate were added and the solution was stirred for 10 minutes at -15° C. 0.14 g (0.44 mmol) of α-(RS)-propyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-methylamine trifluoroacetate was added and the mixture was stirred at room temperature for 66 hours. After evaporation the residue was partitioned between ethyl acetate and 2M hydrochloric acid. The organic layer was washed with 2M hydrochloric acid, water and saturated sodium chloride solution and then dried over anhydrous sodium sulphate. After evaporation there was obtained 0.17 g of N2-[N-[N-[N-[N-[3-(tert-butoxycarbonyl)propionyl]-O-tert-butyl-L-α-aspartyl]-O-tert-butyl-L-α-glutamyl]-2-methyl-L-phenylalanyl]-3-methyl-L-valyl]-N1-N1(RS)-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butyl]-L-leucinamide in the form of a solid; NMR (DMSO, 400 MHz) δ: 0.75-0.9 (m,17H), 1.01-1.08 (m,6H), 1.15-1.25 (m,1H), 1.35 9s,36H), 1.4-1.7 (m,4H), 1.75-1.8 (m,1H), 2.05-2.15 (m,2H), 2.23 (s,3H), 2.29-2.41 (m,6H), 2.55-2.6 (m,1H), 2.7-2.74 (m,1H), 2.95-3.05 (m,1H), 4.15-4.25 (m,3H), 4.48-4.55 (m,1H), 4.6-4.7 (m,1H), 7.05-7.11 (m,4H), 7.7-7.81 (m,2H), 8.05-8.12 (m,2H), 8.15-8.25 (m,2H).

Provenance & Evidence