1,1'-Carbonyldiimidazole → Methyl 4-(3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl)bicyclo[2.2.2]octane-1-carboxylate

HRID 22846Notes

Reaction equation

HRID 22846 reaction equation
[CH3:1][O:2][C:3]([C:5]12[CH2:12][CH2:11][C:8]([C:13](O)=O)([CH2:9][CH2:10]1)[CH2:7][CH2:6]2)=[O:4].C(N1C=CN=C1)(N1C=CN=C1)=O.[F:28][C:29]1[CH:38]=[CH:37][C:32]([C:33](=[N:35][OH:36])[NH2:34])=[CH:31][CH:30]=1>ClCCl>[F:28][C:29]1[CH:38]=[CH:37][C:32]([C:33]2[N:34]=[C:13]([C:8]34[CH2:11][CH2:12][C:5]([C:3]([O:2][CH3:1])=[O:4])([CH2:6][CH2:7]3)[CH2:10][CH2:9]4)[O:36][N:35]=2)=[CH:31][CH:30]=1

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 5930004-Fluoro-n-hydroxybenzimidamideHCID 110420624-(Methoxycarbonyl)bicyclo[2.2.2]octane-1-carboxylic acid

Product 1

HCID 20755118Methyl 4-(3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl)bicyclo[2.2.2]octane-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 4-(methoxycarbonyl)bicyclo[2.2.2]octane-1-carboxylic acid (7-A) (0.906 g, 4.27 mmol) in dichloromethane (20 mL) was added 1,1′-carbonyldiimidazole (1.04 g, 6.41 mmol). The reaction turned into a clear solution instantly with evolving of gas. After the mixture was stirred at room temperature for 1 h, 4-fluorobenzamidoxime was added (1.98 g, 12.8 mmol). Stirring was continued overnight. The mixture was then concentrated and the residue was refluxed in toluene for 16 h. The mixture was concentrated and the residue was purified by column chromatography using hexane/ethyl acetate as eluent (7/1) to give methyl 4-[3-(4-fluorophenyl)-1,2,4-oxadiazol-5-yl]bicyclo[2.2.2]octane-1-carboxylate acid (7-B) as a white solid. 1H NMR (500 MHz, CDCl3) δ 1.96-1.99 (m, 6H), 2.08-2.14 (m, 6H), 3.71 (s, 3H), 7.16-7.20 (m, 2H), 8.08-8.10 (m, 2H) ppm. ESI-MS m/z (M+H) 349.2.

Workup

  1. stirringStirring
  2. waitwas continued overnight
  3. concentrationThe mixture was then concentrated
  4. temperaturethe residue was refluxed in toluene for 16 h
  5. concentrationThe mixture was concentrated
  6. customthe residue was purified by column chromatography

Sources & evidence

ORD record
ord-7c74b71f8b874e618fe1fa7ab2e75271
Source dataset
uspto-grants-2005_02
Patent number
US06849636B2

Reaction notes

Loading…