Reaktion #353896

Reaktionsgleichung

HCl

U-100592

benzyloxyacetylchloride

→

benzyloxyacetic acid

Ausbeute 44.0%

Lösungsmittel

methylene chloride

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwas added dropwise
2. 2
   Sonstigethe resulting layers were separated
3. 3
   ExtraktionThe aqueous layer was extracted with methylene chloride (3×5 mL)
4. 4
   WaschenThe combined organic layers were washed with brine
5. 5
   Trocknendried (MgSO4)
6. 6
   Filtrationthen filtered
7. 7
   Einengenconcentrated to a white solid
8. 8
   workup.DISSOLUTIONThe crude was dissolved in a small amount of methylene chloride and methanol
9. 9
   WaschenThe column was eluted with ethyl acetate, 2% methanol/ethylacetate, 4% methanol/ethyl acetate, 6% methanol/ethyl acetate, 8% methanol/ethyl acetate, and 10% methanol/ethyl acetate (250 mL each)

Vorschrift

To a mixture of 200 mg (0.508 mmol) of U-100592 (Ex. 1), 149 mg (1.47 mmol, 0.205 mL), and 5 mL methylene chloride at 0° C. benzyloxyacetylchloride was added dropwise. The reaction was allowed to warm slowly up to room temperature. After stirring for 5 hours, 5 mL of 1N HCl was added, and the resulting layers were separated. The aqueous layer was extracted with methylene chloride (3×5 mL). The combined organic layers were washed with brine and dried (MgSO4) then filtered and concentrated to a white solid. The crude was dissolved in a small amount of methylene chloride and methanol and was placed on a 22 cm×2.5 cm 40-60 μ silica column. The column was eluted with ethyl acetate, 2% methanol/ethylacetate, 4% methanol/ethyl acetate, 6% methanol/ethyl acetate, 8% methanol/ethyl acetate, and 10% methanol/ethyl acetate (250 mL each). The appropriate fractions were pooled to provide 120 mg (44%) of benzyloxyacetic acid, 2-[-[4-[5-(acetylamino)methyl]-2-oxo-3-oxazolidinyl]-2-fluorophenyl]-1-piperazinyl]-2-oxoethyl ester, (S)-; as a white solid (mp=146°-148° C.).

Quelle