Veratrole → N-Boc-(2,3-dimethoxyphenyl)-4-piperidinylmethanone

HRID 51270

Reaktionsgleichung

Reaktionsgleichung von HRID 51270
[Li]CCCC.[C:6]1([O:14][CH3:15])[C:7](=[CH:10][CH:11]=[CH:12][CH:13]=1)[O:8][CH3:9].COCN[C:20]([CH:22]1[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24][CH2:23]1)=[O:21]>CCCCCC.O1CCCC1>[CH3:9][O:8][C:7]1[C:6]([O:14][CH3:15])=[CH:13][CH:12]=[CH:11][C:10]=1[C:20]([CH:22]1[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24][CH2:23]1)=[O:21]

Komponenten

6

Edukt 3

HCID 7043VeratroleHCID 442032024-(Methoxymethylcarbamoyl)piperidine-1-carboxylic acid tert-butyl esterHCID 178418339Butyllithium

Produkt 1

HCID 46780868N-Boc-(2,3-dimethoxyphenyl)-4-piperidinylmethanone

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittel2×HCID 8058HexaneLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A solution of n-BuLi (2.5M, 452 mL) in hexane was added to a solution of veratrole (149 g, 1.08 mol) in anhydrous tetrahydrofuran (1.2 L) over 10 minutes at −78° C. under nitrogen. The resulting solution was stirred at 0° C. for 1 hour and room temperature for 4 hours. A solution of 4-[(methoxymethylamino)carbonyl]-1-piperidinecarboxylic acid, 1,1-dimethylethyl ester (15) (275 g, 1.01 mol) in tetrahydrofuran (800 mL) was added to the reaction slurry at −65° C. over 20 minutes. The mixture was warmed to room temperature, stirred for 18 hours and quenched with saturated ammonium chloride (1 L). After stirring for 1 hour, the phases were separated and the aqueous layer was extracted with ethyl ether (1 L). The combined organic solutions were washed with brine (2 L) and dried (MgSO4). The mixture was filtered and the filtrate was concentrated (30° C./20 torr) to a residue (413 g). The solution may be used directly in Scheme L, step a, Example 108.

Aufarbeitung

  1. temperatureThe mixture was warmed to room temperature
  2. stirringstirred for 18 hours
  3. customquenched with saturated ammonium chloride (1 L)
  4. stirringAfter stirring for 1 hour
  5. customthe phases were separated
  6. extractionthe aqueous layer was extracted with ethyl ether (1 L)
  7. washThe combined organic solutions were washed with brine (2 L)
  8. dry with materialdried (MgSO4)
  9. filtrationThe mixture was filtered
  10. concentrationthe filtrate was concentrated (30° C./20 torr) to a residue (413 g)

Quellen und Nachweise

ORD-Eintrag
ord-74e44df03d06443bac63a75ca0bbbe91
Quelldatensatz
uspto-grants-2004_03
Patentnummer
US06713627B2

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