Triethylamine → N-[N-[(1S)-1-(Ethoxycarbonyl)-3-phenylpropyl]-N-(2,2,2-trichloroethoxycarbonyl)-L-alanyl]-4-hydroxy-L-proline ethyl ester

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Reaction Steps

To N-[(1S)-1-(ethoxycarbonyl)-3-phenylpropyl]-N-(2,2,2-trichloroethoxycarbonyl)-L-alanine (5.94 g, 13.07 mmol) in 50 ml methylene chloride, under N2, was added oxalyl chloride (5.70 ml, 65.33 mmol) and then N,N-dimethylformamide (20 uL). The solution was stirred 3.5 hours and concentrated in vacuo. The residue was diluted with 30 ml methylene chloride and cooled with an ice bath while under N2. To this solution was added portionwise a mixture of 4-hydroxy-L-proline ethyl ester hydrochloride (1.96 g, 10.05 mmol) and triethylamine (6.99 ml, 50.25 mmol) in 40 ml methylene chloride. After the addition was complete the solution was slowly warmed to room temperature, stirred 18 hours and concentrated in vacuo. The residue was dissolved in ether and washed with water, 10% HCl, 1N NaOH, and brine, and dried (MgSO4) and concentrated in vacuo. Chromatography of the residue on HPLC, using 50% ethyl acetate in hexanes as eluents, provided 2.44 g (41%) of the oily product.

Provenance & Evidence