Hydrogen Peroxide → HCID 86761348, compound

Temperature

0 °C

72.3 ml (72.3 mmol) of dibutylboron triflate and then 12.6 ml (72.3 mmol) of diisopropylethylamine are added dropwise to a solution, cooled to 0° C., of 15.2 g (57.8 mmol) of (S)-4-benzyl-3-(2-ethoxyacetyl)oxazolidin-2-one, prepared as described in the publication by Bernard Hulin et al., J. Med. Chem., 1996, 39, 3897-3907, from commercial (S)-4-benzyloxazolidin-2-one, in 150 ml of dichloromethane. The reaction medium is stirred at 0° C. for 30 min and then cooled to −78° C. A solution of 15 g (48.2 mmol) of tert-butyl (4′-formylbiphenyl-3-yl)methylcarbamate in 70 ml of dichloromethane is then added dropwise. After stirring from −78° C. to ambient temperature over 4 hours, the reaction medium is cooled to 0° C. and a mixture of 130 ml of a buffer solution, pH=7, and of 100 ml of methanol is added dropwise, followed by the dropwise addition of a mixture of 130 ml of aqueous hydrogen peroxide solution and of 100 ml of methanol. The reaction medium is stirred at 0° C. for 1 hour and then at ambient temperature for 3 hours. After addition of water, the reaction medium is extracted with dichloromethane. The organic phase is dried over magnesium sulfate, filtered and evaporated under vacuum. The residue obtained is purified by chromatography on a silica column eluted with a mixture of heptane and ethyl acetate (70/30) and then increase in the polarity up to a 50/50 heptane/ethyl acetate mixture. After evaporation of the solvents, 28 g of tert-butyl {4′-[3-(4(S)-benzyl-2-oxooxazolidin-3-yl)-2(S)-ethoxy-1(R)-hydroxy-3-oxopropyl]biphenyl-3-yl}methylcarbamate are collected. Yield=81%.

1. customprepared
2. temperaturecooled to −78° C
3. stirringAfter stirring from −78° C. to ambient temperature over 4 hours
4. temperaturethe reaction medium is cooled to 0° C.
5. stirringThe reaction medium is stirred at 0° C. for 1 hour
6. waitat ambient temperature for 3 hours
7. extractionthe reaction medium is extracted with dichloromethane
8. dry with materialThe organic phase is dried over magnesium sulfate
9. filtrationfiltered
10. customevaporated under vacuum
11. customThe residue obtained
12. customis purified by chromatography on a silica column
13. washeluted with a mixture of heptane and ethyl acetate (70/30)
14. temperatureincrease in the polarity up to a 50/50 heptane/ethyl acetate mixture
15. customAfter evaporation of the solvents, 28 g of tert-butyl {4′-[3-(4(S)-benzyl-2-oxooxazolidin-3-yl)-2(S)-ethoxy-1(R)-hydroxy-3-oxopropyl]biphenyl-3-yl}methylcarbamate
16. customare collected

ORD record

ord-643398bc1abf4f43b02c02a784afcd87

Source dataset

uspto-grants-2011_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07973063B2