L-Phenylalanine → HCID 70079233, compound

Participants

Reaction Steps

To a solution of Mu-PheOH (1.29 g, 4.63 mmol) in THF (20 mL) were added 4-methylmorpholine (0.51 mL, 4.63 mmol) and isobutyl chloroformate (0.61 mL, 4.63 mmol). After 3 minutes, a solution of (S) 3-amino-1-(4-nitrophenyl)-5-phenyl-1-pentene hydrochloride, prepared by HCl/dioxane-mediated deprotection of (S) 3-tert-butoxycarbonylamino-1-(4-nitrophenyl)-5-phenyl-1-pentene precursor, 1.34 g, 4.20 mmol) in CH2Cl2 (20 mL), followed by 4-methylmorpholine (0.51 mL, 4.63 mmol). The mixture was stirred overnight while warming to room temperature. The solution mixture was diluted with CH2Cl2 (100 mL), washed with 1M HCl (200 mL), saturated aqueous sodium bicarbonate (200 mL); dried over MgSO4, filtered, and concentrated under reduced pressure to give a yellow oil. This material was crystallized from CH2Cl2 /ether (2:100, 20 mL) to give 1.00 g (40%) of (S)-3-(4-morpholinecarbonylphenylalanyl)amino-1-(4-nitrophenyl)-5-phenyl-1-pentene as an approximately 4:1 E/Z mixture. 0.27 g (0.49 mmol) of this material was dissolved in ethanol (50 mL), transferred to a Parr bottle charged with 5% palladium on carbon (0.10 g) and reduced on a Parr hydrogenator for 8 hours/ The mixture was filtered and the solvent was removed under reduced pressure. The residue was dissolved in in 4:1 ether/CH2Cl2 (100 mL), to which HCl/dioxane (0.136 mL of a 4.0M solution) was added. The product, Mu-Phe-Hph-γ-C6H4 NH2.HCl, was filtered and dried in vacuo. Yield=0.15 g (54%). TLC: (10% methanol/CH2Cl2) Rf =0.31.

Provenance & Evidence