Water → HCID 67298368, Verbindung

To a solution of (2S)-2-{(R)-[(4-bromophenyl)-(4-fluorophenyl)-methyl]-amino}-4-methylpentan-1-ol (3.28 g, 8.65 mmol) in acetonitrile (50 mL) containing water (0.375 mL) at 0-5° C. was added, over 20 minutes, a solution of periodic acid and chromium [VI] oxide in acetonitrile (50 mL: prepared by dissolving 11.4 grams of H5IO6 and 23 mg of CrO3 in 100 mL of CH3CN and stirring for 2 hours at room temperature according to the procedure described in Tetrahedron Letters, 1998, vol. 39, p. 5323-5326). The reaction mixture was stirred overnight while warming to room temperature. Disodium phosphate (1.8 g/100 mL water) was added. The reaction mixture was extracted with toluene (150 mL), washed with 1:1 brine/water (50 mL), freshly prepared sodium bisulfate solution (2 g/50 mL water), brine (50 mL), dried over MgSO4, filtered, concentrated in vacuo, and purified on a short plug of silica gel (30% ethyl acetate/hexane elution to remove non-polar impurities, then 50% ethyl acetate/dichloromethane elution) to give (2S)-2-{(R)-[(4-bromophenyl)-(4-fluorophenyl)-methyl]-amino}-4-methylpentanoic acid.

1. additionwas added, over 20 minutes
2. stirringThe reaction mixture was stirred overnight
3. temperaturewhile warming to room temperature
4. extractionThe reaction mixture was extracted with toluene (150 mL)
5. washwashed with 1:1 brine/water (50 mL), freshly prepared sodium bisulfate solution (2 g/50 mL water), brine (50 mL)
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. custompurified on a short plug of silica gel (
10. wash30% ethyl acetate/hexane elution
11. customto remove non-polar impurities
12. wash50% ethyl acetate/dichloromethane elution)

ORD-Eintrag

ord-f8a463ad0ddb4b2280d537ca3c64e366

Quelldatensatz

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08318748B2