1: methanephosphonic acid dimethyl ester With n-butyllithium in tetrahydrofuran; hexane T=-78°C; 0.25 h; Inert atmosphere; 2: N-tert-butoxycarbonyl-L-phenylalanine in tetrahydrofuran; hexane T=-78 - -30°C; 3 h; Inert atmosphere;

1: 100 percent / thionyl chloride / 24 h / 0 - 20 °C 2: nBuLi / tetrahydrofuran / -78 °C View Scheme

1: mixed anhydride method 2: H2 / Pd-C 3: mixed anhydride method 4: HCl / dioxane 5: mixed anhydride method 6: H2 / Pd-C 7: dicyclohexylcarbodiimide (DCCI) 8: trifluoracetic acid (TFA) 9: pyridine View Scheme

1.1: 1,1-carbonyldiimidazole / CH2Cl2 / 0.5 h / 20 °C 1.2: 1,8-diazabicyclo[5.4.0]undec-7-ene / CH2Cl2 / 20 h / 20 °C 2.1: acetyl chloride; methanol / CH2Cl2 / 24 h / 20 °C View Scheme

1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine

1: N-tert-butoxycarbonyl-L-phenylalanine With 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride in N,N-dimethyl-formamide T=0°C; Inert atmosphere; 2: methyl (2R)-2-(t-butoxycarbonylamino)-3-phenylpropionate With 4-methyl-morpholine in N,N-dimethyl-formamide T=20°C; Inert atmosphere;

1: Et3N 2: NaBH4 / methanol 3: 96 percent / Et3N View Scheme

1: 1.) N-methylmorpholine (NMM), isobutyl chloroformate / 1.) THF, -25 deg C, 5 min, 2.) THF, ether, -70 deg C to RT 2: 97 percent / 4 N HCl / dioxane / 1 h / Ambient temperature 3: 1.) hydroxybenzotriazole (HOBt), EDCI, 2.) N-methylmorpholine (NMM) / 1.) DMF, 40 min, 2.) DMF, a) 0 deg C, 2 h, b) RT, overnight 4: 4 N HCl / dioxane / 1 h / Ambient temperature 5: 1.) hydroxybenzotriazole (HOBt), EDCI, 2.) N-methylmorpholine (NMM) / 1.) DMF, 40 min, 2.) DMF, a) 0 deg C, 2 h, b) RT, overnight 6: 4 N HCl / dioxane / 1 h / Ambient temperature 7: 1.) hydroxybenzotriazole (HOBt), EDCI, 2.) N-methylmorpholine (NMM) / 1.) DMF, 40 min, 2.) DMF, a) 0 deg C, 2 h, b) RT, overnight 8: 4 N HCl / dioxane / 1 h / Ambient temperature 9: triethylamine, DCM / dimethylformamide / 2 h / 0 - 20 °C 10: NaI, NaHCO3 / dimethylformamide / 18 h / Ambient temperature 11: NaBH4 / methanol 12: 99 percent / H2 / 10percent Pd(OH)2/C / aq. acetic acid / 4 h View Scheme

1: TEA / tetrahydrofuran / 0.42 h / -15 °C 2: 2.52 g / NH3 / H2O / 3 h / 0 - 5 °C 3: 93 percent / TFAA / pyridine / 2.5 h / 0 °C 4: H2; NH3 / Raney Ni / H2O; ethanol / 4 h / 2250.18 Torr View Scheme

1: 93 percent / HOBT; dicyclohexylcarbodiimide / CH2Cl2 / 0 - 20 °C 2: TFA / CH2Cl2 / 1 h / 20 °C 3: TEA / CH2Cl2 / 2 h / 20 °C View Scheme