Thionyl Chloride → (S)-3-[4-(2,6-dichlorobenzoylamino)phenyl]-2-(2,6-dichloro-4-triisopropylsilanyloxy-benzoylamino)propionic acid methyl ester

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Reaction Steps

To a solution of 2,6-dichloro-4-triisopropylsilanyloxy-benzoic acid (3.63 g, 10 mmol) in toluene (50 mL) was added an excess of thionyl chloride (11.89 g, 7.2 mL, 100 mmol) at room temperature. The resulting colorless solution was heated to reflux for 5 h and then it was cooled to room temperature and the solvent and excess thionyl chloride was removed under vacuum. The resulting residue was azeotrophed one time with toluene. Then, the above 2,6-dichloro-4-triisopropylsilanyloxy-benzoic acid chloride was dissolved in dichloromethane (50 mL) and the solid (S)-2-amino-3-[4-(2,6-dichlorobenzoylamino)phenyl]propionic acid methyl ester hydrochloride salt (4.1 g, 10 mmol) and DIPEA (3.87 g, 5.26 mL, 30 mmol) were added at room temperature. The resulting solution was stirred for 15 h at room temperature and water was added (˜200 mL) to the reaction mixture. Then, the organic compound was extracted into dichloromethane (2×150 mL). The combined organic layer was washed with brine solution and dried over anhydrous MgSO4. Filtration and concentration gave the crude residue which was purified using an ISCO (120 g) column chromatography to obtain 6.48 g (95%) of (S)-3-[4-(2,6-dichlorobenzoylamino)phenyl]-2-(2,6-dichloro-4-triisopropylsilanyloxy-benzoylamino)propionic acid methyl ester as a white solid. ES(+)-HRMS m/e calcd. for C33H38Cl4N2O5Si (M+H)+ 711.1377, obsd. 711.1377.

Provenance & Evidence