Oxalyl chloride → 3-Acetyl-2,2-dimethylcyclobutylacetic acid tert-butyl ester

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Reaction Steps

S-Pinonic acid 5 (39.9 g, 216 mmol) was dissolved in a solution of oxalyl chloride (222 mL, 444 mmol, 2.0 M in CH2Cl2) and a few drops of DMF were then added. The solution was stirred at room temperature for 3 h, and the solvent was removed in vacuo. t-Butanol (389 mL) and DIEA (42.8 mL, 244 mmol) were added and the reaction mixture was stirred at room temperature for 16 hour before removing the solvent in vacuo. EtOAc (500 mL) was added to the slurry and was subsequently washed with H2O (500 mL) and saturated NaHCO3 (500 mL). The aqueous layers were combined and extracted with EtOAc (150 mL×2). The organic layers were combined and dried with brine and MgSO4 concentrated to yield crude 7. The oil was purified by chromatography (hexane-EtOAc, 5:1 to 4:1) to yield 7 (47.8 g, 93%) as a yellow liquid.

Provenance & Evidence