Hydrogen Peroxide → HCID 9822765, compound

The (4S)-3-[2-ethyl-3-[4-methoxy-3-[[N-[4-(trifluoromethyl)phenyl]carbamoyl]methyl]phenyl]propanoyl]-4-benzyloxazolidine-2-one with high polarity (2.65 g, 4.66 mmol) was dissolved into a mixed solvent (4:1 v/v) (23 mL) of tetrahydrofuran with water, and cooled with ice after replacement with argon. Under stirring, 30% aqueous hydrogen peroxide (1.89 mL, 18.6 mmol) was added dropwise over 5 minutes. Following this, lithium hydroxide monohydrate (313 mg, 7.46 mmol) dissolved into water (7.8 mL) was added dropwise over 5 minutes, and the mixture was stirred further for 4 hours under cooling with ice. To the reaction mixture, 64% sodium hydrogensulfite (2.98 g, 18.6 mmol) dissolved into water (12 mL) was added dropwise. The reaction mixture was concentrated and the residue was poured into ice water, which was made acidic by adding 5% hydrochloric acid, and then extracted with methylene chloride. The extracte was washed with brine, then dried over anhydrous magnesium sulfate and concentrated. The residue was dissolved into isopropyl ether under heating and allowed to stand. The precipitated crystals were collected by filtration and dried. Further, after concentration, the filtrate was purified by silica gel column chromatography (eluent: methylene chloride:methanol=20:1→15:1 v/v) to afford 1.37 g (72%) of (+)-2-ethyl-3-[4-methoxy-3-[[N-[4-(trifluoromethyl)-phenyl]carbamoyl]methyl]phenyl]propanoic acid as colorless crystalline powder.

1. temperaturecooled with ice after replacement with argon
2. additionwas added dropwise over 5 minutes
3. stirringthe mixture was stirred further for 4 hours
4. temperatureunder cooling with ice
5. additionwas added dropwise
6. concentrationThe reaction mixture was concentrated
7. additionthe residue was poured into ice water, which
8. additionby adding 5% hydrochloric acid
9. extractionextracted with methylene chloride
10. washThe extracte was washed with brine
11. dry with materialdried over anhydrous magnesium sulfate
12. concentrationconcentrated
13. dissolutionThe residue was dissolved into isopropyl ether
14. temperatureunder heating
15. filtrationThe precipitated crystals were collected by filtration
16. customdried
17. concentrationFurther, after concentration
18. customthe filtrate was purified by silica gel column chromatography (eluent: methylene chloride:methanol=20:1→15:1 v/v)

ORD record

ord-0fac47199c95453790be95832f6686a6

Source dataset

uspto-grants-2006_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07049342B2