Methyl (R)-(+)-2-isocyanato-3-phenylpropionate → (R)-2-(4-Phenoxymethyl-benzyloxycarbonylamino)-3-phenyl-propionic Acid Methyl Ester

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Reaction Steps

(R)-Phenylalanine methyl ester hydrochloride (6.5 g, 30 mmol) was dissolved in methylene chloride and cooled to 0C. Phosgene (2M in toluene, 21.0 ml, 42.0 mmol) was added followed by pyridine (9.0 ml, 111 mmol). The mixture was allowed to warm to room temperature and was stirred for three hours. The mixture was then poured into dilute HCl. The layers were separated. The organic extracts were washed, dried, and concentrated to give about 5.8 g of a clear oil of (R)-2-isocyanato-3-phenyl-propionic acid methyl ester 5. 4-Phenoxymethylphenylmethanol 4 (0.857 g, 4.0 mmol), (R)-2-isocyanato-3-phenyl-propionic acid methyl ester 5 (1.026 g, 5.0 mmol) and 4-dimethylaminopyridine (DMAP) (10 mg) were combined, heated until molten, and stirred for 20 min. Upon cooling, the residue was purified by chromatography to give about 1.6 g of (R)-2-(4-phenoxymethyl-benzyloxycarbonylamino)-3-phenyl-propionic acid methyl ester 6.

Provenance & Evidence