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

HRID 448227

Reaktionsgleichung

Reaktionsgleichung von HRID 448227
[C:1]([O:5][C:6]([NH:8][CH:9]([CH2:14][CH:15]([C:19]1[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=1)[C:16](=O)[CH3:17])[C:10](OC)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])(=O)C.[NH4+].C(O)(=O)C.C([BH3-])#[N:36].[Na+].C(=O)(O)[O-].[Na+].C(=O)([O-])[O-].[K+].[K+]>CO.O.C(O)C>[C:1]([O:5][C:6](=[O:7])[NH:8][CH:9]1[CH2:14][CH:15]([C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=2)[CH:16]([CH3:17])[NH:36][C:10]1=[O:11])([CH3:4])([CH3:3])[CH3:2]

Komponenten

10

Edukt 6

HCID 176Acetic AcidHCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 517165Ammonium AcetateHCID 5003444Sodium cyanoborohydrideHCID 68747752Methyl 2-[(tert-butoxycarbonyl)amino]-4-(4-chlorophenyl)-5-oxohexanoate

Produkt 1

HCID 86665200tert-Butyl [5-(4-chlorophenyl)-6-methyl-2-oxopiperidin-3-yl]carbamate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 702EthanolLösungsmittelHCID 887MethanolLösungsmittelHCID 962WaterLösungsmittel2×

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

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, 584 mmol), acetic acid (50.2 mL, 876 mmol), and sodium cyanoborohydride (5.51 g, 87.7 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. MS: m/z=361.2 (M+Na).

Aufarbeitung

  1. temperatureto cool to ambient temperature
  2. extractionThe mixture was extracted with ethyl acetate (3×)
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. extractionfollowed by extraction with ethyl acetate (3×)
  8. washThe combined organic extracts were washed with brine
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customPurification by silica gel chromatography (100% dichloromethane→90% dichloromethane/methanol with 0.1% ammonium hydroxide)

Quellen und Nachweise

ORD-Eintrag
ord-f59a692deb384689a8230f7c393b790b
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08481556B2

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