Chlorotrimethylsilane → 2-(2-Chloro-benzoylamino)-butyric acid

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Reaction Steps

This compound was prepared according to the procedures described in Int. J. Peptide Protein Res. 1989, 33, 353, and J. Chem. Soc., Chem. Commun. 1995, 2335. 2-Amino-butyric acid (3.87 g, 37.5 mmol) was suspended in 90 mL of dichloromethane, and treated with chloro-trimethyl-silane (9.6 mL, 75 mmol). The mixture was refluxed for 1 h and cooled in an ice bath. Diisopropylethylamine (11.3 mL, 65 mmol) and 2-chloro-benzoyl chloride (4.3 mL, 35.6 mmol) were added. The solution was stirred with cooling for 20 min and then warmed up to room temperature for 1.5 h. The mixture was concentrated and then distributed between ether and diluted NaHCO3 solution. The phases were separated. The aqueous layer was extracted with ether and the ether layer was back washed with water. The combined aqueous layers were acidified to pH 2 with 1N HCl and extracted with ethyl acetate three times. The combined ethyl acetate layers were dried over sodium sulfate, filtered and concentrated to give 2-(2-chloro-benzoylamino)-butyric acid as an off-white solid (7.0 g, 77% yield), which was used directly in the next step without further purification. LCMS calcd for C11H12ClNO3 (m/e) 241, obsd 242 (M+H).

Provenance & Evidence