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

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.

1. temperaturethe mixture was cooled to 0°
2. stirringAfter another 10 min of stirring
3. washwashed with chloroform (3×)
4. additionby the addition of solid citric acid
5. extractionextracted with EtOAc (3×)
6. washThe combined EtOAc extracts were washed with brine
7. dry with materialdried (Na2SO 4)
8. concentrationconcentrated to dryness

ORD record

ord-5e74dda20ebc46e78cceaac946a9446a

Source dataset

uspto-grants-1996_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05565476