Dimethylformamide → HCID 7350179, compound

Participants

Reaction Steps

BOC-Phe (manufactured and sold by PEPTIDE INSTITUTE INC., Japan, 10.6 g) was dissolved in 100 ml of ethyl acetate, to thereby obtain a solution. To the obtained solution were added 10.0 g of phenacyl bromide and 5.1 g of triethylamine while cooling over ice, followed by stirring. The reaction temperature was elevated to room temperature, followed by stirring overnight to effect a reaction, thereby obtaining a reaction mixture. The obtained reaction mixture was evaporated to dryness, to thereby obtain a residue. The obtained residue was dissolved in 50 ml of ethyl acetate and the resultant solution was washed with a saturated aqueous sodium hydrogencarbonate solution and then with saturated saline. The washed solution was dried with magnesium sulfate and concentrated under reduced pressure, to thereby obtain 13.4 g of BOC-Phe phenacyl ester. Further, to 1.9 g of BOC-Phe phenacyl ester was added 5 ml of trifluoroacetic acid (TFA), followed by stirring for 10 minutes. The resultant reaction mixture was evaporated to dryness under reduced pressure for removing TFA, to thereby obtain a residue. To the obtained residue were added 20 ml of DMF, 0.61 g of N-methylmorpholine, 1.24 g of DCC, 0.81 g of HOBT and BOC-Gly (manufactured and sold by PEPTIDE INSTITUTE INC., Japan 1.05 g), followed by stirring overnight at room temperature, to thereby obtain a reaction mixture. The obtained reaction mixture was concentrated under reduced pressure, to thereby obtain a residue. The obtained residue was dissolved in 50 ml of ethyl acetate, and the resultant solution was washed with 0.1 N hydrochloride cooled with ice, saturated saline, a saturated aqueous sodium hydrogencarbonate solution and again saturated saline successively. The washed solution was dried with magnesium sulfate and concentrated under reduced pressure, to thereby obtain 1.5 g of BOC-Gly-Phe phenacyl ester. Further, to 1.6 g of BOC-Gly-Phe phenacyl ester was added 5 ml of trifluoroacetic acid (TFA), followed by stirring for 10 minutes, to thereby obtain a reaction mixture. The obtained reaction mixture was evaporated to dryness under reduced pressure for removing TFA, to thereby obtain a residue. To the obtained residue were added 20 ml of DMF, 0.40 g of N-methylmorpholine, 0.83 g of DCC, 0.54 g of HOBT and 0.84 g of Z-Gly (manufactured and sold by Kokusan Chemical Works Ltd., Japan), followed by stirring overnight at room temperature, to thereby obtain a reaction mixture. The obtained reaction mixture was concentrated under reduced pressure, to thereby obtain a residue. The obtained residue was dissolved in 50 ml of ethyl acetate and the resultant solution was washed with 0.1 N solution hydrochloride cooled with ice, saturated saline, a saturated aqueous sodium hydrogencarbonate solution and again saturated saline successively. The washed solution was dried with magnesium sulfate and concentrated under reduced pressure, to thereby obtain 1.1 g of Z-Gly-Gly-Phe phepacyl ester. 1.1 g of Z-Gly-Gly-Phe phenacyl ester was dissolved in 30 ml of 90% acetic acid, to obtain a mixture. To the obtained mixture was added 4 g of zinc dust, followed by stirring at room temperature for 5 hours, to thereby obtain a reaction mixture. The obtained reaction mixture was subjected to filtration and evaporated to dryness, to thereby obtain a residue. The obtained residue was dissolved in 30 ml of ethyl acetate and the resultant solution was washed with 10% citric acid and then with saturated saline successively, dried with magnesium sulfate and concentrated under reduced pressure, to thereby obtain 0.62 g of Z-Gly-Gly-Phe.

Provenance & Evidence