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

HRID 1068454Notes

Reaction equation

HRID 1068454 reaction equation
[C:1]([C:3]1[CH:16]=[CH:15][C:6]([CH2:7][N:8]2[C:12]([CH2:13]O)=[CH:11][N:10]=[CH:9]2)=[CH:5][CH:4]=1)#[N:2].FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.Cl.[CH3:33][C:34]1[CH:35]=[C:36]([CH:48]=[CH:49][CH:50]=1)[CH2:37][C:38]1([C:44]([O:46][CH3:47])=[O:45])[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]1.C(N(C(C)C)CC)(C)C>ClCCl>[C:1]([C:3]1[CH:16]=[CH:15][C:6]([CH2:7][N:8]2[C:12]([CH2:13][N:41]3[CH2:42][CH2:43][C:38]([CH2:37][C:36]4[CH:48]=[CH:49][CH:50]=[C:34]([CH3:33])[CH:35]=4)([C:44]([O:46][CH3:47])=[O:45])[CH2:39][CH2:40]3)=[CH:11][N:10]=[CH:9]2)=[CH:5][CH:4]=1)#[N:2]

Participants

6

Reactant 4

HCID 67749Trifluoromethanesulfonic anhydrideHCID 81531DiisopropylethylamineHCID 101982471-(4-Cyanobenzyl)-5-hydroxymethyl-1H-imidazoleHCID 21193291Methyl 4-(3-methylbenzyl)piperidine-4-carboxylate hydrochloride salt

Product 1

HCID 15410567Methyl 1-[3-(4-cyanobenzyl)-3H-imidazol-4-ylmethyl]-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-ylmethyl alcohol (184 mg, 0.81 mmol) and dilsopropylethylarnine (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-720d85343b5f4410be2c9b9cb706a556
Source dataset
uspto-grants-2001_06
Patent number
US06248756B1

Reaction notes

Loading…