Sodium Bicarbonate → HCID 66933922, compound

Participants

Reaction Steps

To a solution of n-BuLi (1.6 M solution in hexane, 17 mL, 27 mmol) in THF (50 mL), maintained at 0° C. under nitrogen atmosphere, hexamethyldisilazane (5.7 mL, 27 mmol) was added dropwise and stirred for 15 min. To this, a solution of the compound of example (36)(5.6 g, 10 mmol) in THF (50 mL) was added drop wise, 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, and basified with 10% sodium bicarbonate to pH 8-9. The aqueous layer was extracted with chloroform (3×75 mL). The organic layer was washed with water (50 mL), brine (50 mL) and dried over anhydrous Na2SO4. The organic layer was concentrated under reduced pressure and dried under vacuum to yield acetic acid 3-{3-[3-(2-chloro-4-cyano-phenyl)-3-oxo-propionyl]-2-hydroxy-4,6-dimethoxy-phenyl}-1-methyl-pyrrolidin-2-ylmethyl ester as oil (6.1 g). This ester was dissolved in conc. HCl (60 mL) and stirred for 3 hrs. to effect cyclisation. At the end of 3 hrs, the reaction mixture was basified with solid NaHCO3 to pH 8-9. The aqueous layer was extracted with chloroform (50×3 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 0.01% ammonia as eluent to yield the compound, (+)-trans-2-(2-chloro-4-cyano-phenyl)-8-(2-hydroxymethyl-1-methyl-pyrrolidin-3-yl)-5,7-dimethoxy-chromen-4-one, as a yellow solid.

Provenance & Evidence