Ammonium Acetate → 4-[1-Hydroxy-5-(2-fluoropyridin-4-yl)-4-(3-trifluoromethylphenyl)-1H-imidazol-2-yl]piperidine-1-carboxylic acid benzyl ester

HRID 862209Notes

Reaction equation

HRID 862209 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([C:8](=[N:21][OH:22])[C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:20])([F:19])[F:18])[CH:12]=2)=O)[CH:5]=[CH:4][N:3]=1.[CH2:23]([O:30][C:31]([N:33]1[CH2:38][CH2:37][CH:36]([CH:39]=O)[CH2:35][CH2:34]1)=[O:32])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C([O-])(=O)C.[NH4+:45]>C(O)(=O)C>[CH2:23]([O:30][C:31]([N:33]1[CH2:38][CH2:37][CH:36]([C:39]2[N:21]([OH:22])[C:8]([C:6]3[CH:5]=[CH:4][N:3]=[C:2]([F:1])[CH:7]=3)=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:20])([F:19])[F:18])[CH:12]=3)[N:45]=2)[CH2:35][CH2:34]1)=[O:32])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

5

Reactant 3

HCID 517165Ammonium AcetateHCID 2776272Benzyl 4-formylpiperidine-1-carboxylateHCID 1363810621-(2-Fluoropyridin-4-yl)-2-(3-trifluoromethylphenyl)ethane-1,2-dione-1-oxime

Product 1

HCID 537036274-[1-Hydroxy-5-(2-fluoropyridin-4-yl)-4-(3-trifluoromethylphenyl)-1H-imidazol-2-yl]piperidine-1-carboxylic acid benzyl ester

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
75 °C

Procedure

To a mixture of 1-(2-fluoropyridin-4-yl)-2-(3-trifluoromethylphenyl)ethane-1,2-dione-1-oxime (11.4 g, 0.037 mole) and N-benzyloxycarbonylpiperidin-4-carboxaldehyde [Amici et al Eur. J. Med. Chem. 26, 625-631 (1991)] (9.93 g, 0.040 mol), in acetic acid (250 mL) was added ammonium acetate (56.29 g, 0.730 mole). The mixture was heated to 75° C. for 1 h, cooled and concentrated to remove most of the acetic acid. The residue was poured into concentrated NH4OH (100 mL), ice (200 g) and methylene chloride (800 mL) and the pH adjusted to 8 with NH4OH. The methylene chloride layer was removed and the aqueous layer washed with methylene chloride (2×300 mL). The combined organic phases were washed with water (300 mL), brine (300 mL), dried over anhydrous sodium sulfate, filtered and concentrated to give an oil used in the next step without further purification.

Workup

  1. temperaturecooled
  2. concentrationconcentrated
  3. customto remove most of the acetic acid
  4. additionThe residue was poured into concentrated NH4OH (100 mL), ice (200 g) and methylene chloride (800 mL)
  5. customThe methylene chloride layer was removed
  6. washthe aqueous layer washed with methylene chloride (2×300 mL)
  7. washThe combined organic phases were washed with water (300 mL), brine (300 mL)
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto give an oil
  12. customused in the next step without further purification

Sources & evidence

ORD record
ord-25772ce11e29429f848fe2d60fe9a494
Source dataset
uspto-grants-1998_02
Patent number
US05717100

Reaction notes

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