Hydrochloric Acid → HCID 87384391, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of n-BuLi (15% solution in hexane, 8.2 mL, 19.25 mmol) in THF (30 mL), maintained at 0° C. under nitrogen atmosphere, hexamethyldisilazane (4.06 mL, 19.9 mmol) was added drop wise and stirred for 15 minutes. To this, a solution of compound of example 31 (3.8 g, 7.75 mmol) in THF (30 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 hours. 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 obtain acetic acid 3-{3-[3-(3-chloro-phenyl)-3-oxo-propionyl]-2-hydroxy-4,6-dimethoxy-phenyl}-1-methyl-pyrrolidin-2-ylmethyl ester as an oil (2.7 g), which was dissolved in conc. HCl (60 mL) and stirred for 3 hours to effect cyclisation. At the end of 3 hours, 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 afford the title compound.

Provenance & Evidence