Reaktion #427354

Reaktionsgleichung

potassium carbonate

sodium bicarbonate

methyl 2-[(tert-butoxycarbonyl)amino]-4-(4-chlorophenyl)-5-oxohexanoate

ammonium acetate

acetic acid

sodium cyanoborohydride

→

title compound

tert-Butyl[5-(4-chlorophenyl)-6-methyl-2-oxopiperidin-3-yl]carbamate

Lösungsmittel

Ethanol

water

Water

methanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturto cool to ambient temperature
2. 2
   ExtraktionThe mixture was extracted with ethyl acetate (3×)
3. 3
   WaschenThe combined organic extracts were washed with brine
4. 4
   Trocknendried over magnesium sulfate
5. 5
   Filtrationfiltered
6. 6
   Einengenconcentrated
7. 7
   Extraktionfollowed by extraction with ethyl acetate (3×)
8. 8
   WaschenThe combined organic extracts were washed with brine
9. 9
   Trocknendried over magnesium sulfate
10. 10
    Filtrationfiltered
11. 11
    Einengenconcentrated
12. 12
    SonstigePurification by silica gel chromatography (100% dichloromethane→90% dichloromethane/methanol with 0.1% ammonium hydroxide)

Vorschrift

To a solution of methyl 2-[(tert-butoxycarbonyl)amino]-4-(4-chlorophenyl)-5-oxohexanoate (21.6 g, 58.4 mmol) in methanol (200 mL) were added ammonium acetate (45.0 g, 58.4 mmol), acetic acid (50.2 mL, 876 mmol), and sodium cyanoborohydride (5.51 g, 88 mmol). The mixture was heated at 60° C. for a total of 4 h. The mixture was then allowed to cool to ambient temperature and sodium bicarbonate and water were added. The mixture was extracted with ethyl acetate (3×). The combined organic extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated. Ethanol (240 mL) and potassium carbonate (40.4 g, 292 mmol) were added. The mixture was stirred 1.5 h at 60° C. to effect epimerization to the desired epimer. Water was added followed by extraction with ethyl acetate (3×). The combined organic extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% dichloromethane→90% dichloromethane/methanol with 0.1% ammonium hydroxide) gave the title compound as a mixture of isomers (12.3 g). MS 361.2 (M+Na).

Quelle