Triethylamine hydrochloride → [4-(3-Hydroxypyrrolidinyl)-2-phenylbenzoyl]methionine methyl ester

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Reaction Steps

A solution of 4-chloromethyl-2-phenylbenzoic acid methyl ester (0.521 g, 2.00 mmol), prepared as in Example 286A, 3-pyrrolidinol (0.178 g, 2.00 mmol), K2CO3 (0.553 g, 4.00 mmol), and Bu4NI (0.0754 g, 0.20 mmol) in CH3CN (5 mL) was stirred for 15 hours, treated with LiOH.H2O (0.506 g, 12.0 mmol), and then heated at reflux for 5 hours. The solution was cooled to ambient temperature and added to a mixture of L-methionine methyl ester hydrochloride (0.807 g, 4.00 mmol), 3-hydroxy-1,2,3-benzotriazin-4(3H)-one (1.66 g, 10.00 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (1.96 g, 10.00 mmol), and triethylamine hydrochloride (2.81 g, 20 mmol) in CH3CN (15 mL). After 12 days the mixture was concentrated under reduced pressure and the residue was dissolved in ethyl acetate. The solution was extracted with a 1:1 mixture of H2O and saturated aqueous NaHCO3 (4×) and brine. The organic phase was dried (MgSO4) and concentrated to provide a gold oil. Radial chromatography (12% methanol-ethyl acetate) afforded the desired compound (0.494 g, 56%).

Provenance & Evidence