Dicyclohexylcarbodiimide → HCID 67313135, compound

Participants

Reaction Conditions

Reaction Steps

(5-Acetyl-thiophen-2-yl)-acetic acid (2 g, 10.8 mmol), 3-hydroxymethyl-3-methyloxetane (1.07 mL, 10.8 mmol), and dimethylaminopyridine (221 mg, 1.08 mmol) were dissolved in 5 mL of dry THF and cooled to 0° C. Dicyclohexylcarbodiimide (2.24 g, 10.8 mmol) was added and the mixture was stirred at 0° C. for 1 hr, then warmed to room temperature and stirred overnight. The mixture was cooled to 0° C. and filtered. The white solid was washed with cold THF and the combined filtrates were concentrated. The crude product was purified via flash chromatography (hexanes/ethyl acetate gradient) to give 2.3 g of (5-Acetyl-thiophen-2-yl)-acetic acid 3-methyl-oxetan-3-ylmethyl ester (8.5 mmol, 79%). The product was dissolved in 20 mL DCM and cooled to −5° C. Boron trifluoride diethyletherate (121 μL, 1 mmol) was added dropwise, the mixture was slowly warmed to room temperature and stirred for 30 minutes. The reaction was quenched with triethylamine, concentrated and purified via flash chromatography (hexanes/ethyl acetate gradient) to give 1.44 g of 1-[5-(4-Methyl-2,6,7-trioxa-bicyclo[2.2.2]oct-1-ylmethyl)-thiophen-2-yl]-ethanone (4.1 mmol, 38% over two steps).

Provenance & Evidence