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

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

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).