Imidazole → (3-Cyano-cyclohexyl)-carbamic acid tert-butyl ester

HRID 1257716Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1257716
P(Cl)(Cl)(Cl)=O.N1C=CN=C1.[C:11]([O:15][C:16](=[O:27])[NH:17][CH:18]1[CH2:23][CH2:22][CH2:21][CH:20]([C:24](=O)[NH2:25])[CH2:19]1)([CH3:14])([CH3:13])[CH3:12]>N1C=CC=CC=1>[C:11]([O:15][C:16](=[O:27])[NH:17][CH:18]1[CH2:23][CH2:22][CH2:21][CH:20]([C:24]#[N:25])[CH2:19]1)([CH3:14])([CH3:12])[CH3:13]

Komponenten

5

Edukt 3

HCID 795ImidazoleHCID 24813Phosphorus oxychlorideHCID 67324654(1R,3S)-3-(Boc-amino)cyclohexanecarboxamide

Produkt 1

HCID 67323270(3-Cyano-cyclohexyl)-carbamic acid tert-butyl esterAusbeute 69,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1049PyridineLösungsmittel

Versuchsvorschrift

To a mixture of phosphorus oxychloride (4.60 g, 30.0 mmol) and imidazole (1.22 g, 18.0 mmol) in pyridine (40 mL) cooled in an ice-methanol bath was slowly added (3-carbamoyl-cyclohexyl)-carbamic acid tert-butyl ester (1.45 g, 6.00 mmol). The reaction was stirred for 3 hours, allowing to warm to room temperature. The suspension was filtered, the filtrate evaporated and the solids combined before partitioning between aq. NH4Cl (30 mL) and EtOAc (3×30 mL). The combined organic layers were dried (MgSO4) and evaporated to give 930 mg (69%) of (3-cyano-cyclohexyl)-carbamic acid tert-butyl ester as a gum, which was used directly in the next step. 1H NMR (400 MHz, CDCl3) δ: 4.53-4.29 (m, 1H), 3.50-3.33 (m, 1H), 2.58-2.44 (m, 1H), 2.42-2.33 (m, 1H), 2.09-1.99 (m, 1H), 1.99-1.77 (m, 3 h), 1.44 (s, 9H), 1.39-1.30 (m, 2H), 1.18-1.02 (m, 1H).

Aufarbeitung

  1. temperaturecooled in an ice-methanol bath
  2. filtrationThe suspension was filtered
  3. customthe filtrate evaporated
  4. custombefore partitioning between aq. NH4Cl (30 mL) and EtOAc (3×30 mL)
  5. dry with materialThe combined organic layers were dried (MgSO4)
  6. customevaporated

Quellen und Nachweise

ORD-Eintrag
ord-fa678c78c21640a29d37f2d712434f26
Quelldatensatz
uspto-grants-2013_06
Patentnummer
US08461328B2

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