Ethyl chloroformate → (+/-)-2-[(Acetylthio)methyl]-4-methyl-N-[2-(4-morpholinyl)ethyl]pentanamide

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Reaction Conditions

Reaction Steps

2-[(Acetylthio)methyl]-4-methylpentanoic acid (2.0 g) is dissolved in 40 ml of tetrahydrofuran (THF) and 1.0 g of triethylamine. This solution is cooled to -5° C. and ethyl chloroformate in 5 ml of THF is added dropwise. The reaction mixture is stirred at -5° C. for 20 minutes and then N-(2-aminoethyl)morpholine [1.3 g] in 20 ml of THF is added dropwise. It is stirred at 20° C. for 4 hours and stored at 0° C. for about 16 hours. Triethylamine hydrochloride is filtered off and the filtrate is concentrated in vacuo. This residue is dissolved in ether and washed once with aqueous NaHCO3 and twice with water. The ether is dried with MgSO4, filtered and concentrated in vacuo to yield 1.6 g of material. This is purified by dissolving 0.6 g in 2 ml of ether and placing it on top of a pad of alumina (activity II 10 g). The column is washed through with 250 ml of ether which is concentrated in vacuo. Product crystallizes and is washed with 1:5 ether-pentane. The remainder of the crude is seeded with a small crystal and then washed with 1:5 ether-pentane. Total yield is 1.0 g of the title compound, melting point 54°-59° C.

Provenance & Evidence