Sodium Sulfate → Tert-butyl 4-(5-chloro-2-methoxyphenyl)-4-hydroxypiperidine-1-carboxylate

HRID 46310

Reaktionsgleichung

Reaktionsgleichung von HRID 46310
Br[C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[O:9][CH3:10].C([Li])CCC.[C:16]([N:23]1[CH2:28][CH2:27][C:26](=[O:29])[CH2:25][CH2:24]1)([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17].S([O-])(O)(=O)=O.[Na+].S([O-])([O-])(=O)=O.[Na+].[Na+]>O1CCCC1.CCCCCC>[Cl:8][C:6]1[CH:5]=[CH:4][C:3]([O:9][CH3:10])=[C:2]([C:26]2([OH:29])[CH2:25][CH2:24][N:23]([C:16]([O:18][C:19]([CH3:21])([CH3:20])[CH3:22])=[O:17])[CH2:28][CH2:27]2)[CH:7]=1

Komponenten

8

Edukt 5

HCID 24436Sodium SulfateHCID 516919Sodium BisulfateHCID 5219352-Bromo-4-chloroanisoleHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 178418339Butyllithium

Produkt 1

HCID 58772480Tert-butyl 4-(5-chloro-2-methoxyphenyl)-4-hydroxypiperidine-1-carboxylateAusbeute 39 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittel2×HCID 8058HexaneLösungsmittel

Reaktionsbedingungen

Temperatur
-70 °C

Versuchsvorschrift

To a stirred solution of 2-bromo-4-chloroanisole (164 g, 0.74 mol) in tetrahydrofuran (1 L), cooled at −70° C. and under an atmosphere of argon, was added butyl lithium (2.7 M in heptane, 280 ml) over a period of 1 hour. The mixture was stirred for 30 minutes, maintaining the temperature at −70° C., before the addition of N-boc-4-piperidone (145 g, 0.73 mol) in tetrahydrofuran (250 ml) over a period of 1 hour. The reaction temperature was warmed to −40° C. over 2 hours before the addition of sodium hydrogen sulphate (5M aqueous, 160 ml), sodium sulphate (300 g) and hexane (500 ml). The mixture was stirred for 10 hours. The organic layer was decanted, filtered through silica gel (300 g, 63/100 μm) washing with ethyl acetate:hexane (4:6, by volume, 2×400 ml). The filtrate was evaporated in vacuo and the residue recrystallized from ethyl acetate:hexane to afford the title compound as white crystals, 100 g, 39% yield.

Aufarbeitung

  1. stirringThe mixture was stirred for 10 hours
  2. customThe organic layer was decanted
  3. filtrationfiltered through silica gel (300 g, 63/100 μm)
  4. washwashing with ethyl acetate:hexane (4:6, by volume, 2×400 ml)
  5. customThe filtrate was evaporated in vacuo
  6. customthe residue recrystallized from ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-eee2c5700986480da74e4c1a25da7e63
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08541588B2

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