Hydrogen Peroxide → 2(R)-(cyclopropylmethyl)butanedioic acid

Participants

Reaction Steps

3(R)-(Cyclopropylmethy)-4-{[1(S)-(cyclohexylmethyl)-2(R),3(S)-dihydroxy-5-methylhexyl]amino}-butanoic Acid tert-Butyl Ester: A solution of the latter oxazolidinone derivative (10.2 g, 30 mmol) in THF/H2O (150 mL /20 mL) was cooled to 0° . A 30% aqueous solution of H2O2 (9.5 mL, 90 mmol of H2O2) was added to the cooled solution. Thereafter, an aqueous 1M solution of LiOH (30 mL, 30 mmol of LiOH) was added dropwise at 0° over a 5 min period. The stirred mixture was allowed to warm to room temperature. After being stirred at room temperature for 3 h, the mixture was cooled to 0° and an aqueous 1M solution of Na2SO3 (135 mL, 135 mmol) was added over a period of 10 min. After another 10 min of stirring, the mixture was diluted with H2O and washed with chloroform (3×). The aqueous layer was rendered acidic (pH 4) by the addition of solid citric acid and extracted with EtOAc (3×). The combined EtOAc extracts were washed with brine, dried (Na2SO 4) and concentrated to dryness to give the desired monoprotected dicarboxylic acid, i.e. the 4 -tert-butyl ester of 2(R)-(cyclopropylmethyl ) butanedioic acid, as a colorless oil (6.65 g, 97%); [α]D23 +16.1° (c 2.61, CHCl3). The monoprotected dicarboxylic acid was used for the following coupling step without purification.

Provenance & Evidence