Acetonitrile → 4-Mercapto-4-methylpentanoic acid

Participants

Reaction Conditions

Reaction Steps

A 500 mL flask was equipped with a stir bar and a 150 mL addition funnel. The system was placed under an argon atmosphere, and charged with anhydrous tetrahydrofuran (150 mL) and 2.5 M n-BuLi (75 mL, 18.7 mmol) in hexanes (18.7 mmol). The solution was cooled to −78° C. using a dry ice/acetone bath. Acetonitrile (7.3 g, 9.4 mL, 18 mmol) was added drop-wise via a syringe over approximately 5 min. The reaction was stirred for 30 min, while white lithium-acetonitrile precipitate was formed. Isobutylene sulfide (12), (15 g, 17 mmol) was dissolved in 100 mL of anhydrous THF and added dropwise over approximately 30 min via the addition funnel. The cooling bath was removed and the reaction was allowed to stir for 3 hours. The flask was cooled in an ice/water bath as of 0.5 M HCl (38 mL) was added drop-wise. The THF layer was retained and the aqueous layer was washed twice with 75 mL of ethyl acetate. The THF and ethyl acetate layers were combined, dried over approximately 20 g of anhydrous sodium sulfate and transferred to a 250 mL flask. Solvent was removed by rotary evaporation under vacuum to give crude 13. Ethanol (30 mL) was added, and the contents were stirred as a solution of NaOH (8.0 g) in deionized water (30 mL) was slowly added. The flask was equipped with a reflux condenser and placed under an argon atmosphere. The reaction was refluxed overnight and then cooled to room temperature. Deionized water (60 mL) was added and the mixture was washed with 2:1 (v/v) ethyl acetate:hexanes (2×25 mL). The aqueous layer was acidified to pH 2 with concentrated HCl, and then extracted with ethyl acetate (3×75 mL). The organic layers were dried over anhydrous sodium sulfate, filtered, and the solvent was removed by rotary evaporation under vacuum to give 10 g of product 14 (39% yield). The product was used without further purification. 1H NMR (CDCl3): δ 1.38 (6H, s), 1.87-1.93 (2H, m), 2.08 (1H, s), 2.51-2.57 (2H, m).

Provenance & Evidence