Dichloromethane → 4-[5-(4-Cyanobenzyl)imidazol-1-ylmethyl]-1-phenyl-2-piperidinone hydrochloride

HRID 1739002Notes

Reaction equation

HRID 1739002 reaction equation
O[CH2:2][CH:3]1[CH2:8][CH2:7][N:6]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:5](=[O:15])[CH2:4]1.C([N:35]1[CH:39]=[C:38]([CH2:40][C:41]2[CH:46]=[CH:45][C:44]([C:47]#[N:48])=[CH:43][CH:42]=2)[N:37]=[CH:36]1)(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(N(C(C)C)CC)(C)C.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.C(Cl)[Cl:74]>>[ClH:74].[C:47]([C:44]1[CH:43]=[CH:42][C:41]([CH2:40][C:38]2[N:37]([CH2:2][CH:3]3[CH2:8][CH2:7][N:6]([C:9]4[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=4)[C:5](=[O:15])[CH2:4]3)[CH:36]=[N:35][CH:39]=2)=[CH:46][CH:45]=1)#[N:48]

Participants

6

Reactant 5

HCID 6344DichloromethaneHCID 67749Trifluoromethanesulfonic anhydrideHCID 81531DiisopropylethylamineHCID 154282234-(Hydroxymethyl)-1-phenylpiperidin-2-oneHCID 158375331-Trityl-4-(4-cyanobenzyl)imidazole

Product 1

HCID 218400234-[5-(4-Cyanobenzyl)imidazol-1-ylmethyl]-1-phenyl-2-piperidinone hydrochloride

Conditions

Temperature
-78 °C

Procedure

The product from Step D (0.205 g, 1.00 mmol) and the product from Step E (0.425 g, 1.00 mmol) were dissolved in methylene chloride (2 mL) containing diisopropylethylamine (0.191 mL, 1.10 mmol) and cooled to -78° C. under argon. Trifluoromethane sulfonic anhydride was added (0.173 mL, 1.03 mmol) and the reaction stirred at -78° C. for 1 h, followed by warming to room temperature over 2 h. The solvent was evaporated, and the residue dissolved in methanol. After refluxing for 30 min, the methanol was evaporated, and the residue is partitioned between ethyl acetate and saturated sodium bicarbonate solution. The organic phase is washed with saturated brine, dried over magnesium sulfate, filtered and concentrated. The free base product was chromatographed on silica gel with 3% methanol in methylene chloride follwed by 7% 9:1 methanol:ammonium hydroxide in methylene chloride. The title compound was obtained after conversion to the hydrochloride salt. FAB ms: 371 (M+1). Anal. Calc for C23H22N4O·HCl·H2O, C, 65.01; H, 5.93; N,13.19. Found: C, 64.77; H, 5.89; N, 13.11.

Workup

  1. temperatureby warming to room temperature over 2 h
  2. customThe solvent was evaporated
  3. dissolutionthe residue dissolved in methanol
  4. temperatureAfter refluxing for 30 min
  5. customthe methanol was evaporated
  6. customthe residue is partitioned between ethyl acetate and saturated sodium bicarbonate solution
  7. washThe organic phase is washed with saturated brine
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe free base product was chromatographed on silica gel with 3% methanol in methylene chloride

Sources & evidence

ORD record
ord-8c183aa16e51406ea75bb8768e00143a
Source dataset
uspto-grants-1999_10
Patent number
US05965578

Reaction notes

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