Reaktion #493732

Reaktionsgleichung

triethylamine

sodium bicarbonate

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

hydrogen

triethylamine

di-tert-butyl dicarbonate

→

title compound

tert-Butyl [(3S,5S,6R)-6-methyl-2-oxo-5-phenylpiperidin-3-yl]carbamate

Lösungsmittel

Ethanol

methanol

Dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   FiltrationThe mixture was filtered
2. 2
   Einengenconcentrated
3. 3
   Filtrationwas filtered
4. 4
   Einengenconcentrated
5. 5
   workup.STIRRINGthe mixture was stirred for 30 min
6. 6
   Extraktionthe mixture was extracted with dichloromethane (2×)
7. 7
   WaschenThe combined organic extracts were washed with brine
8. 8
   Trocknendried over magnesium sulfate
9. 9
   Filtrationfiltered
10. 10
    Einengenconcentrated
11. 11
    SonstigePurification by silica gel chromatography (100% dichloromethane→90% dichloromethane/methanol with 0.1% ammonium hydroxide)

Vorschrift

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).

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