Methyl iodide → 1-benzyl-4-(1-methyl-1H-tetrazol-5-yl)-4-(N-phenylpropionamido)piperidine

HRID 2350921Notes

Reaction equation

HRID 2350921 reaction equation
[C:1]([O-])(=O)CC.[CH2:6]([NH+:13]1[CH2:18][CH2:17][C:16]([C:30]2[NH:34][N:33]=[N:32][N:31]=2)([N:19]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:20](=[O:23])[CH2:21][CH3:22])[CH2:15][CH2:14]1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[H-].[Na+].IC>CN(C=O)C>[CH2:6]([N:13]1[CH2:18][CH2:17][C:16]([C:30]2[N:34]([CH3:1])[N:33]=[N:32][N:31]=2)([N:19]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:20](=[O:23])[CH2:21][CH3:22])[CH2:15][CH2:14]1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 178460016HCID 178460016, compound

Product 1

HCID 147739911-benzyl-4-(1-methyl-1H-tetrazol-5-yl)-4-(N-phenylpropionamido)piperidineYield 27.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirring mixture of 1-benzyl-4-(1H-tetrazol-5-yl)-4-(N-phenylpropionamido)piperidinium propionate (18.9 g, 40.7 mmol) and DMF (120 ml), NaH (2.4 g, 100 mmol) was added. The mixture was stirred at room temperature for 30 minutes. To the resulting brown solution, iodomethane (15 g, 106 mmol) was added slowly. It was stirred for 30 minutes and poured onto H2O (400 ml). The mixture was extracted with CH2Cl2 (2×250 ml). The CH2Cl2 solution was washed with H2O (4×400 ml), dried over Na2SO4 and concentrated in vacuo. The resulting residue was chromatographed (SiO2, 1% MeOH/CH2Cl2) to give 1-benzyl-4-(1-methyl-1H-tetrazol-5-yl)-4-(N-phenylpropionamido)piperidine (4.58 g, 11.3 mmol) as a colorless viscous oil: IR (neat) 1660 cm-1 ; NMR (270 MHZ, CDCl3) δ0.834, (t, 3H, CH3CH2CO), 1.789 (q, 2H, CH3CH2), 3.334 (s, 2H, phCH2), 4.435 (s, 3H, tetrazolyl CH3), 7.15 to 7.47 (m's, 10H, phenyl H's), and 1-benzyl-4-(2-methyl-2H-tetrazol-5-yl)-4-(N-phenylpropionamido)piperidine (2.75 g, 6.8 mmol) as a viscous oil: IR (neat) 1660 cm-1 ; NMR (270 MHz, CDCl3) δ0.830 (t, 3H, CH3CH2CO), 1.810 (q, 2H, CH3CH2), 3.402 (s, 2H, phCH2), 4.369 (s, 3H, tetrazolyl CH3), 7.20 to 7.54 (3m's, 10H, phenyl H's). ##STR29##

Workup

  1. additionwas added
  2. stirringIt was stirred for 30 minutes
  3. additionpoured onto H2O (400 ml)
  4. extractionThe mixture was extracted with CH2Cl2 (2×250 ml)
  5. washThe CH2Cl2 solution was washed with H2O (4×400 ml)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe resulting residue was chromatographed (SiO2, 1% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-b816fd3831834331ab3a8c07f356dc81
Source dataset
uspto-grants-1989_10
Patent number
US04871749

Reaction notes

Loading…