Benzyl Bromide → 4-((2-Benzyl)tetrazol-5-yl)piperidine

HRID 1068178Notes

Reaction equation

HRID 1068178 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[NH:18][N:17]=[N:16][N:15]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.[H-].[Na+].[CH2:21](Br)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>CN(C=O)C>[CH2:21]([N:17]1[N:16]=[N:15][C:14]([CH:11]2[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]2)=[N:18]1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 18187701Tert-butyl 4-(2H-tetrazol-5-YL)piperidine-1-carboxylate

Product 1

HCID 181874764-((2-Benzyl)tetrazol-5-yl)piperidine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 438 mg (1.7 mmol) of 1-(t-butoxycarbonyl)-4-(1H-tetrazol-5-yl)piperidine (from Step B) in 2 mL of DMF at 0° C. was treated with 83 mg (0.50 mmol) of NaH (60% in mineral oil) and 0.41 mL (3.4 mmol) of benzyl bromide. The resulting mixture was warmed to rt and stirred for 2.5 h. The mixture was partitioned between 50 mL of ether and 50 mL of water and the layers were separated. The organic layer was washed with 50 mL sat'd NaCl, dried over MgSO4 and concentrated. Flash chromatography using 2:1 v/v CH2Cl2/ether, then 1:2 v/v CH2Cl2/ether afforded 85 mg (15%) of 1-butoxycarbonyl)-4-((2-benzyl)tetrazol-5-yl)piperidine. Elution with 2:1 v/v EtOAc/CH2Cl2 afforded 95 mg (17%) of 1-butoxycarbonyl)-4-((1-benzyl)tetrazol-5-yl)piperidine. For 1-(butoxycarbonyl)-4-((2-benzyl)tetrazol-5-yl)piperidine: 1H NMR (500 MHz) δ1.47 (s, 9H), 1.76-1.84 (2H), 2.02-2.05 (2H), 2.91-2.95 (2H), 3.07-3.12 (m, 1H), 4.00-4.20 (2H), 5.71 (s, 2H), 7.35-7.40 (5H). For 1-(butoxycarbonyl)-4-((1-benzyl)tetrazol-5-yl)piperidine: 1H NMR (500 MHz) δ1.45 (s, 9H), 1.59-1.61 (2H), 1.76-1.84 (2H), 2.70-2.80 (2H), 2.85-2.89 (m, 1H), 4.00-4.20 (2H), 5.55 (s, 2H), 7.17-7.19 (2H), 7.36-7.39 (3H).

Workup

  1. customThe mixture was partitioned between 50 mL of ether and 50 mL of water
  2. customthe layers were separated
  3. washThe organic layer was washed with 50 mL sat'd NaCl
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-323d06ed51f24b2ebd0f7d3852cac06a
Source dataset
uspto-grants-2001_06
Patent number
US06248755B1

Reaction notes

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