1,1'-Carbonyldiimidazole → 1-[3-(5-Hydroxy-2,2,4-trimethyl-7-pentyl-2H-1-benzopyran-3-yl)-1-oxopropoxy]-2,5-pyrrolidinedione

Participants

Reaction Steps

Alternate Synthesis To a solution of 100 mg (0.30 mmol) of the acid 5-Hydroxy-2,2,4-trimethyl-7-pentyl-2H-1-benzopyran-3-propanoic acid in 15 mL of anhy. THF under argon and cooled in an ice-water bath was added 150 mg (3 eq) of carbonyldiimidazole (CDI) (Fluka Chem. Co.) as a solid in one lot. The reaction was stirred at ~0° C. for ~1 hr. The ice bath was removed and the stirred reaction allowed to warm up to RT over 1.5 hr. To the reaction was then added 345 mg (10 eq) of N-hydroxysuccinimide (NHS) (Aldrich) as a solid in one lot and the reaction stirred at RT under argon for 18 hrs. The reaction mixture was then evaporated under reduced pressure and the residue partitioned between 100 mL of EtOAc and 30 mL of 0.1N aq. HCl. The phases were separated and the organic layer washed with 0.1N HCl (2×30 mL), water (1×30 mL), 50 mM phosphate buffer pH 8 (3×30 mL), sat. aq. NaCi (1×30 mL), dried (Na2SO4), evaporated under reduced pressure and the residue dried under high vacuum. The residue was then subjected to PLC, eluting with 50% EtOAc-CH2Cl2. The upper product band was isolated and the silica washed with EtOAc. The washings were evaporated under reduced pressure and dried under high vacuum to give 44 mg of the desired product 1-[3-(5-Hydroxy-2,2,4-trimethyl-7-pentyl-2H-1-benzopyran-3-yl)-1-oxopropoxy]-2,5-pyrrolidinedione as a glass/amorphous solid.

Provenance & Evidence