Trifluoromethanesulfonic anhydride → methyl 1-[3-(4-cyanobenzyl)-3H-imidazol-4-ylethyl]-4-(3-methylbenzyl)piperidine-4-carboxylate

Temperature

-78 °C

To a cold (-78° C.) solution of 3-(4-cyanobenzyl)-3H-imidazol-4-ylethyl alcohol (184 mg, 0.81 mmol) and diisopropylethylamine (155 μL, 0.89 mmol) in dichloromethane (3.8 mL), trifluoromethanesulfonic anhydride (143 μL, 0.85 mmol) was added. The resulting mixture was stirred at -78° C. for 20 min., and was treated with a solution of methyl 4-(3-methylbenzyl)piperidine-4-carboxylate hydrochloride salt (276 mg, 0.97 mmol; Example 61, Step B) and diisopropylethylamine (186 μL, 1.07 mmol) in dichloromethane (1 mL). The reaction mixture was stirred at -78° C. for one h., and at room temp. for two h. The resultant solution was concentrated under vacuum, and the residue was partitioned between dichloromethane and aqueous sodium bicarbonate. The organic extract was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The crude product was subjected to high pressure liquid column chromatography on C-18 reverse phase stationary phase. Collection and lyophilization of appropriate fractions provided the title compound as white solid.

1. stirringThe reaction mixture was stirred at -78° C. for one h.
2. waitat room temp. for two h
3. concentrationThe resultant solution was concentrated under vacuum
4. customthe residue was partitioned between dichloromethane and aqueous sodium bicarbonate
5. extractionThe organic extract
6. washwas washed with brine
7. dry with materialdried over anhydrous sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated under vacuum
10. customCollection and lyophilization of appropriate fractions

ORD record

ord-93d64bade0fa4b0b809f09db1b3fa067

Source dataset

uspto-grants-1999_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05891889