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

HRID 443271Notes

Reaction equation

HRID 443271 reaction equation
[C:1]([C:3]1[CH:17]=[CH:16][C:6]([CH2:7][N:8]2[C:12]([CH2:13][CH2:14]O)=[CH:11][N:10]=[CH:9]2)=[CH:5][CH:4]=1)#[N:2].C(N(C(C)C)CC)(C)C.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.Cl.[CH3:43][C:44]1[CH:45]=[C:46]([CH:58]=[CH:59][CH:60]=1)[CH2:47][C:48]1([C:54]([O:56][CH3:57])=[O:55])[CH2:53][CH2:52][NH:51][CH2:50][CH2:49]1>ClCCl>[C:1]([C:3]1[CH:17]=[CH:16][C:6]([CH2:7][N:8]2[C:12]([CH2:13][CH2:14][N:51]3[CH2:52][CH2:53][C:48]([CH2:47][C:46]4[CH:58]=[CH:59][CH:60]=[C:44]([CH3:43])[CH:45]=4)([C:54]([O:56][CH3:57])=[O:55])[CH2:49][CH2:50]3)=[CH:11][N:10]=[CH:9]2)=[CH:5][CH:4]=1)#[N:2]

Participants

6

Reactant 4

HCID 67749Trifluoromethanesulfonic anhydrideHCID 81531Diisopropylethylamine2×HCID 110751433-(4-cyanobenzyl)-3H-imidazol-4-ylethyl alcoholHCID 21193291Methyl 4-(3-methylbenzyl)piperidine-4-carboxylate hydrochloride salt

Product 1

HCID 54084377methyl 1-[3-(4-cyanobenzyl)-3H-imidazol-4-ylethyl]-4-(3-methylbenzyl)piperidine-4-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-93d64bade0fa4b0b809f09db1b3fa067
Source dataset
uspto-grants-1999_04
Patent number
US05891889

Reaction notes

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