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

Temperature

75 °C

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.

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

ORD record

ord-25772ce11e29429f848fe2d60fe9a494

Source dataset

uspto-grants-1998_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05717100