Morpholine → HCID 11035009, compound

In substantially the same manner as Working Example 2, morpholine (1.64 ml, manufactured by Tokyo Kasei) was condensed with Boc-L-phenylalanine (5.00 g) to give Boc-L-phenylalanylmorpholine (6.00 g) as a white powdery product (yield 95%). Taking a portion (2.00 g) of this product, the Boc group was deprotected with TFA, followed by concentration to dryness. The concentrate was dissolved in water, and the solution was allowed to pass through IRA-402 (Cl type, 250 ml, manufactured by Amberlite Inc.), and the solution was concentrated and lyophilized to give L-phenylalanylmorpholine hydrochloride (1.68 g) as a white powdery product (yield: quantitative). A portion (923 mg) of this product was dissolved in dichloromethane (23 ml). To the solution were added, under ice-cooling, (2S,3S)-ethyl hydrogen N-Z-aziridine-2,3-dicarboxylate produced in Working Example 1 (Compound 1, 1.00 g), HOBT (507 mg), WSC (719 mg) and triethylamine (1.02 ml). The mixture was stirred for 14 hours at room temperature. The reaction mixture was concentrated, to which was added ethyl acetate. The mixture was washed with a 10% aqueous solution of citric acid, water, a saturated aqueous solution of sodium hydrogen carbonate, a 2% aqueous solution of sodium hydrogen carbonate, water and a saturated aqueous saline solution, respectively, followed by drying over anhydrous sodium sulfate, which was concentrated. The concentrate was subjected to a silica gel column chromatography (100 ml). The column was subjected to elution with solutions prepared by adding ethyl acetate to hexane in sequence. The eluate with 60% to 70% (v/v) ethyl acetate was concentrated to give the above-titled compound (Compound 8; 940 mg) as a white powdery product (yield 54%).

ORD record

ord-eace188b430b482d84a86bebe181ca3b

Source dataset

uspto-grants-1997_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05668128