Carbon Dioxide → 1,1-Dimethylethyl 4-[3-[(4-methoxyphenyl)methyl]-1,2,4-oxadiazol-5-yl]-1-piperidinecarboxylate

HRID 1992066Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1992066
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([OH:16])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N1C=CN=C1)(N1C=CN=C1)=O.C(=O)=O.O/[N:33]=[C:34](\[NH2:44])/[CH2:35][C:36]1[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][CH:37]=1>CN(C=O)C.CCOC(C)=O>[CH3:43][O:42][C:39]1[CH:40]=[CH:41][C:36]([CH2:35][C:34]2[N:33]=[C:14]([CH:11]3[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:13][CH2:12]3)[O:16][N:44]=2)=[CH:37][CH:38]=1

Komponenten

7

Edukt 4

HCID 280Carbon DioxideHCID 682631,1'-CarbonyldiimidazoleHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acidHCID 5356867N-Hydroxy-2-(4-methoxy-phenyl)-acetamidine

Produkt 1

HCID 587285131,1-Dimethylethyl 4-[3-[(4-methoxyphenyl)methyl]-1,2,4-oxadiazol-5-yl]-1-piperidinecarboxylate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

1-(tert-Butoxycarbonyl)piperidine-4-carboxylic acid (2.29 g, 10.0 mmoles) in 10 mL DMF was treated with 1,1′-carbonyldiimidazole (1.62 g, 10 mmoles, 1 eq.) at ambient temperature for 30 min until CO2 evolution ceased. (1Z)-N′-hydroxy-2-(4-methoxyphenyl)ethanimidamide [J. Med. Chem., 36(11), 1529 (1993)] (10.0 mmoles, 1 eq.) was dissolved in 5 mL DMF and added to the reaction mixture. The reaction mixture was heated at 70° C. for 6 h then at 120° C. for an additional 6 h. The reaction mixture was diluted with EtOAc and washed successively with water, 1N citric acid, saturated aqueous NaHCO3, and brine. The organic phase was isolated, dried over MgSO4, filtered and concentrated to give the title compound as an amber oil. 1H NMR (300 MHz, CDCl3) δ 7.26 (d, 2H, J=8.5 Hz), 6.88 (d, 2H, J=8.5 Hz), 4.10 (m, 2H), 4.00 (s, 2H), 3.80 (s, 3H), 3.08 (m, 1H), 2.97-2.90 (m, 2H), 2.04 (m, 2H), 1.87-1.73 (m, 2H), 1.47 (s, 9H). ES-LCMS m/z 395.99 (M+Na).

Aufarbeitung

  1. additionadded to the reaction mixture
  2. washwashed successively with water, 1N citric acid, saturated aqueous NaHCO3, and brine
  3. customThe organic phase was isolated
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-6280f2a4d5f64ec7a1b0a24737615dda
Quelldatensatz
uspto-grants-2010_01
Patentnummer
US07645771B2

Notizen zur Reaktion

Wird geladen…