1,2-Dichloroethane → {4-Chloro-2-[2-(1-methyl-2-oxo-2-piperidin-1-yl-ethoxy)-benzyl]-phenoxy}-acetic acid methyl ester

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Reaction Steps

To a solution of PS-EDC (0.558 g, 1.42 mmol/g, 0.792 mmol) in DMF (2 mL) is added 2-[2-(5-chloro-2-methoxycarbonylmethoxy-benzyl)-phenoxy]-propionic acid (Intermediate B) (150 mg, 0.396 mmol) in DMF (2 mL) and HOAT (80.8 mg, 0.594 mmol) in DMF (2 mL). The reaction mixture is agitated for 50 minutes and then treated with piperidine (39.2 μL, 0.396 mmol) and agitated at RT for 2 days. Polymer supported trisamine (0.475 g, 1.42 mmol/g, 1.98 mmol) is then added and the mixture is further agitated overnight. The reaction mixture is filtered to remove the resins and rinsed with methanol and DCM. The filtrate is reduced in vacuo and the crude solid is re-dissolved in DCM and washed with water. The organic portion is separated using a phase separator and concentrated in vacuo to yield a solid which is purified by chromatography on silica eluting with EtOAc/iso-hexane (30% increasing to 50% EtOAc) to yield the titled product as a pale yellow oil; MH+=446.

Provenance & Evidence