Diisopropylamine → 4-[2-(2,5-Dichloro-pyrimidin-4-yl)-1-hydroxy-ethyl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1184717Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1184717
[Li+].CCC[CH2-].C(NC(C)C)(C)C.[Cl:13][C:14]1[N:19]=[C:18]([CH3:20])[C:17]([Cl:21])=[CH:16][N:15]=1.[C:22]([O:26][C:27]([N:29]1[CH2:34][CH2:33][CH:32]([CH:35]=[O:36])[CH2:31][CH2:30]1)=[O:28])([CH3:25])([CH3:24])[CH3:23]>O1CCCC1>[C:22]([O:26][C:27]([N:29]1[CH2:34][CH2:33][CH:32]([CH:35]([OH:36])[CH2:20][C:18]2[C:17]([Cl:21])=[CH:16][N:15]=[C:14]([Cl:13])[N:19]=2)[CH2:31][CH2:30]1)=[O:28])([CH3:25])([CH3:24])[CH3:23]

Komponenten

6

Edukt 4

HCID 7912DiisopropylamineHCID 61028n-Butyl lithiumHCID 1514430tert-Butyl 4-formylpiperidine-1-carboxylateHCID 212786212,5-Dichloro-4-methylpyrimidine

Produkt 1

HCID 866749004-[2-(2,5-Dichloro-pyrimidin-4-yl)-1-hydroxy-ethyl]-piperidine-1-carboxylic acid tert-butyl ester

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
-70 °C

Versuchsvorschrift

N-butyllithium (1.6 M in hexanes, 4.99 mL) is added drop wise to diisopropylamine (1.13 mL) in tetrahydrofuran (20 mL) at −50 to −60° C. under an argon atmosphere. The mixture is stirred for 30 min at this temperature, cooled to −70° C., and 2,5-dichloro-4-methyl-pyrimidine (1.00 g) is added. After 1 h a solution of 4-formyl-piperidine-1-carboxylic acid tert-butyl ester (1.37 g) in tetrahydrofuran (10 mL) is added and the resulting mixture is stirred for another hour. The reaction is quenched with acetic acid solution (1% in ethanol, 10 mL) and the mixture is diluted with ethyl acetate. The organic phase is separated, washed with water and aqueous NaHCO3 solution, dried over MgSO4, and concentrated in vacuo. The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 75:25→30:70) to give the title compound. LC (method 7): tR=1.40 min; Mass spectrum (ESI+): m/z=376 [M+H]+.

Aufarbeitung

  1. stirringthe resulting mixture is stirred for another hour
  2. customThe reaction is quenched with acetic acid solution (1% in ethanol, 10 mL)
  3. additionthe mixture is diluted with ethyl acetate
  4. customThe organic phase is separated
  5. washwashed with water and aqueous NaHCO3 solution
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customThe residue is chromatographed on silica gel (cyclohexane/ethyl acetate 75:25→30:70)

Quellen und Nachweise

ORD-Eintrag
ord-b5fc272293fe4153bbf46a8c8d7de8ba
Quelldatensatz
uspto-grants-2014_03
Patentnummer
US08669271B2

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