4-Chlorobenzoyl chloride → 4-(4-Chloro-benzoylamino)-4-cyano-piperidine-1-carboxylic acid tert-butyl ester

HRID 913331Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 913331
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([NH2:16])([C:14]#[N:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:17][C:18]1[CH:26]=[CH:25][C:21]([C:22](Cl)=[O:23])=[CH:20][CH:19]=1.[OH-].[Na+]>ClCCl.C(N(CC)CC)C>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][C:11]([NH:16][C:22](=[O:23])[C:21]2[CH:25]=[CH:26][C:18]([Cl:17])=[CH:19][CH:20]=2)([C:14]#[N:15])[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Komponenten

6

Edukt 3

HCID 85014-Chlorobenzoyl chlorideHCID 14798Sodium HydroxideHCID 22091429tert-Butyl 4-amino-4-cyanopiperidine-1-carboxylate

Produkt 1

HCID 674023234-(4-Chloro-benzoylamino)-4-cyano-piperidine-1-carboxylic acid tert-butyl ester

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8471TriethylamineLösungsmittel

Versuchsvorschrift

To a solution of 4-amino-4-cyano-piperidine-1-carboxylic acid tert-butyl ester (1.25 g, 5.55 mmol, 1.0 equiv; prepared as described in WO 03/104 236 A1 (Bristol-Myers Squibb Company); [CAS RN 331281-25-5]) in dichlormethane (30 mL) and triethylamine (1.20 mL) was added 4-chloro-benzoyl chloride (1.09 g, 6.21 mmol, 1.12 equiv; commercially available) and the reaction stirred at rt overnight. A solution of 1 M NaOH (10 mL) was added and the reaction mixture extracted with ethyl acetate. The combined organic phases were washed with water and a sat. solution of NaCl, dried over MgSO4 and concentrated by evaporation under reduced pressure. The crude material was crystallized from a mixture of hexane/ethyl acetate yielding 0.71 g (44%) of the title compound as white crystals. 1H NMR (300 MHz, CDCl3): δ 1.46 (s, 9H), 1.85 (t, J=10.2 Hz, 2H), 2.45 (br s, 2H), 3.24 (t, J=11.8 Hz, 2H), 3.99 (br d, J=13.5 Hz, 2H), 6.87 (s, 1H), 7.36 (d, J=8.4 Hz, 2H), 7.69 (d, J=8.4 Hz, 2H). MS (ISP): 364.4 [M+H]+.

Aufarbeitung

  1. extractionthe reaction mixture extracted with ethyl acetate
  2. washThe combined organic phases were washed with water
  3. dry with materiala sat. solution of NaCl, dried over MgSO4
  4. concentrationconcentrated by evaporation under reduced pressure
  5. customThe crude material was crystallized from a mixture of hexane/ethyl acetate yielding 0.71 g (44%) of the title compound as white crystals

Quellen und Nachweise

ORD-Eintrag
ord-4af19b52fa8f4fd1add11ce359b56a10
Quelldatensatz
uspto-grants-2011_09
Patentnummer
US08026365B2

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