4-Methylmorpholine → Methyl N-{[5-(3-[(1S)-2-methoxy-1-methylethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenyl)-1H-pyrrol-2-yl]carbonyl}-L-serinate

Participants

Reaction Steps

5-(3-[(1S)-2-Methoxy-1-methylethoxy]-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}phenyl)-1H-pyrrole-2-carboxylic acid (1.60 g, 3.58 mmol) synthesized in Example (78k), L-serine methyl ester hydrochloride (0.61 g, 3.94 mmol), HOBT•H2O (0.53 g, 3.94 mmol) and N-methylmorpholine (0.79 mL, 7.17 mmol) were dissolved in a mixed solvent of methylene chloride (30 mL) and N,N-dimethylformamide (7 mL), and WSCI•HCl (0.82 g, 4.30 mmol) was added at room temperature, followed by stirring for 15 hours under nitrogen atmosphere. The reaction solution was diluted with methylene chloride (100 mL), washed with 1N hydrochloric acid, a saturated aqueous sodium hydrogencarbonate solution and saturated brine, and subsequently dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=50%-80%) to afford the desired compound (1.91 g, 97%) as a white solid.

Provenance & Evidence