Sodium Bicarbonate → HCID 68513538, compound

Participants

Reaction Steps

To a solution of n-BuLi (15% in hexane, 2.54 mL, 5.8 mmol) in THF (25 mL), maintained at 0° C. under nitrogen atmosphere, hexamethyldisilazane (1.25 mL, 5.8 mmol) was added dropwise and stirred for 15 min. To this, a solution of (−)-trans-2-chloro-4-nitro-benzoic acid 2-(2-acetoxymethyl-1-methyl-pyrrolidin-3-yl)-6-acetyl-3,5-dimethoxy-phenyl ester (1.6 g, 3 mmol) in THF (25 mL) was added dropwise, maintaining the temperature at 0° C. After the addition, the reaction was allowed to warm to room temperature and stirred for 2.5 hrs. The reaction mixture was acidified with dilute HCl, basified with 10% NaHCO3 solution to pH 8 to 9. The aqueous layer was extracted with chloroform (3×50 mL). The organic layer was washed with water (25 mL), brine (25 mL), dried over anhydrous Na2SO4. The organic layer was concentrated under reduced pressure and under vacuum to yield acetic acid 3-{3-[3-(2-chloro-4-nitro phenyl)-3-oxopropionyl]-2-hydroxy-4,6-dimethoxyphenyl}-1-methylpyrrolidin-2-ylmethyl ester as a yellow solid (1.6 g). This ester was dissolved in conc. HCl (16 mL) and stirred at room temperature for 3 hrs to effect cyclisation. At the end of 3 hrs, the reaction mixture was basified with solid NaHCO3 to pH 8 to 9. The aqueous layer was extracted with chloroform (3×50 mL) and washed with water (25 mL) and brine (25 mL). The organic layer was dried over anhydrous Na2SO4, concentrated under reduced pressure and dried over vacuum. The residue was purified by column chromatography with 3% methanol in chloroform and 0.1% ammonia as eluent to yield the title compound as a yellow solid.

Provenance & Evidence