Triethylamine → tert-butyl N-((3S,5S,6R)-6-methyl-2-oxo-5-phenylpiperidin-3-yl)carbamate

HRID 1404498

Reaktionsgleichung

Reaktionsgleichung von HRID 1404498
[C:1]([O:5][C:6](=[O:23])[NH:7][CH:8]1[CH2:13][CH:12]([C:14]2[CH:19]=[CH:18][C:17](Cl)=[CH:16][CH:15]=2)[CH:11]([CH3:21])[NH:10][C:9]1=[O:22])([CH3:4])([CH3:3])[CH3:2].[H][H].C(N(CC)CC)C.C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O.C(=O)(O)[O-].[Na+]>CO.[Pd].ClCCl.C(O)C>[C:1]([O:5][C:6](=[O:23])[NH:7][C@H:8]1[CH2:13][C@@H:12]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[C@@H:11]([CH3:21])[NH:10][C:9]1=[O:22])([CH3:3])([CH3:2])[CH3:4]

Komponenten

10

Edukt 5

HCID 8471Triethylamine2×HCID 90495Di-tert-butyl dicarbonateHCID 516892Sodium BicarbonateHCID 86665200tert-Butyl [5-(4-chlorophenyl)-6-methyl-2-oxopiperidin-3-yl]carbamateHCID 178418361HCID 178418361, Verbindung

Produkt 1

HCID 69096668tert-butyl N-((3S,5S,6R)-6-methyl-2-oxo-5-phenylpiperidin-3-yl)carbamate

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 23938PalladiumKatalysator2×HCID 702EthanolLösungsmittelHCID 887MethanolLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of tert-butyl[5-(4-chlorophenyl)-6-methyl-2-oxopiperidin-3-yl]carbamate (12.1 g, 35.7 mmol) in methanol (179 mL) was added 10% palladium on activated carbon (7.6 g, 7.1 mmol). The resulting mixture stirred 6.5 h under 1 atmosphere of hydrogen. The mixture was filtered and concentrated. Ethanol (180 mL), triethylamine (4.98 mL, 35.7 mmol) and 10% palladium on activated carbon (7.6 g, 7.1 mmol) added. The mixture was stirred 2 h 15 min under hydrogen atmosphere at a pressure of 50 psi and then was filtered and concentrated. Dichloromethane (350 mL), triethylamine (2.49 mL, 17.9 mmol), and di-tert-butyl dicarbonate (2.07 mL, 8.93 mmol) were added, and the mixture was stirred for 30 min. Saturated aqueous sodium bicarbonate was added and the mixture was extracted with dichloromethane (2×). 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. The mixture was purified by HPLC (Chiral Pak® AD column, 60% ethanol/hexanes with 0.1% diethylamine). Purification by reverse chromatography (C-18, 90% water/acetonitrile→5% water/acetonitrile with 0.1% trifluoroacetic acid) gave the title compound. MS: m/z=327.3 (M+Na).

Aufarbeitung

  1. filtrationThe mixture was filtered
  2. concentrationconcentrated
  3. filtrationwas filtered
  4. concentrationconcentrated
  5. stirringthe mixture was stirred for 30 min
  6. extractionthe mixture was extracted with dichloromethane (2×)
  7. washThe combined organic extracts were washed with brine
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customPurification by silica gel chromatography (100% dichloromethane→90% dichloromethane/methanol with 0.1% ammonium hydroxide)

Quellen und Nachweise

ORD-Eintrag
ord-85af69c36f98401c9911444abab77799
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08912210B2

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