Sodium hydride → 2-Chloro-5-cyclopentyl-5-hydroxy-3-oxo-non-8-ynoic Acid Methyl Ester

Participants

Reaction Steps

A slurry of NaH (3.2 g, 60% suspension in mineral oil, 80 mmol) in dry THF (250 mL) was cooled to −40° C. Methyl-2-chloroacetoacetate (9.74 mL, 80 mmol) was added slowly. The reaction was stirred until all gas evolution had ceased, and then butyl lithium (2.5 M, 32 mL, 80 mmol) was added. The reaction was stirred for 10 minutes, and then 1-cyclopentyl-pent-4-yn-1-one (4.0 g, 27 mmol) from Step 2 above, was added as a solution in 20 mL THF. The reaction was stirred 1 hour, and then warmed to room temperature. The reaction was quenched with 1 N HCl (200 mL) and the layers were separated. The aqueous layer was extracted with CH2Cl2 and the organic layers were combined. The organic layer was washed with water, and then concentrated by rotary evaporation. The crude product was purified by chromatography to yield the pure product (6.345 g, 78% yield).

Provenance & Evidence