Isopropyl iodide → (1R)-1-{1-[2-(1-methylethyl)-2H-tetrazol-5-yl]-4-piperidinyl}ethanol

HRID 423709Notes

Reaction equation

HRID 423709 reaction equation
[NH:1]1[C:5]([N:6]2[CH2:11][CH2:10][CH:9]([C@H:12]([OH:14])[CH3:13])[CH2:8][CH2:7]2)=[N:4][N:3]=[N:2]1.C(=O)([O-])[O-].[K+].[K+].I[CH:22]([CH3:24])[CH3:23]>CN(C=O)C.CC(C)=O>[CH3:23][CH:22]([N:3]1[N:2]=[N:1][C:5]([N:6]2[CH2:11][CH2:10][CH:9]([C@H:12]([OH:14])[CH3:13])[CH2:8][CH2:7]2)=[N:4]1)[CH3:24]

Participants

6

Reactant 3

HCID 6362Isopropyl iodideHCID 11430Potassium CarbonateHCID 178462231HCID 178462231, compound

Product 1

HCID 66673304(1R)-1-{1-[2-(1-methylethyl)-2H-tetrazol-5-yl]-4-piperidinyl}ethanolYield 72.3%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

A solution of (1R)-1-[1-(1H-tetrazol-5-yl)-4-piperidinyl]ethanol (256 mg, 1.3 mmol) in DMF (1 mL) and acetone (5 mL) was treated with potassium carbonate (359 mg, 2.59 mmol) at room temperature. After stirring for 15 min, 2-iodopropane (661 mg, 3.89 mmol) was added and the mixture was heated at 50° C. for 3 h. The salt was removed by filtration and washed by EtOAc. After concentration, the crude product was purified by chromatography on a silica gel column using MeOH/CH2Cl2 gradient (2.5% to 12.5%) to give 225 mg (69%) of (1R)-1-{1-[2-(1-methylethyl)-2H-tetrazol-5-yl]-4-piperidinyl}ethanol. 1H NMR (400 MHz, CDCl3): δ 4.85 (septet, 1H, J=6.8 Hz), 4.24-4.07 (m, 2H), 3.63 (quint, 1H, J=6.2 Hz), 2.94-2.81 (m, 2H), 2.00-1.89 (m, 1H), 1.76-1.68 (m, 1H), 1.59 (d, 6H, J=6.8 Hz) 1.53-1.31 (m, 4H), 1.22 (d, 3H, J=6.2 Hz).

Workup

  1. customThe salt was removed by filtration
  2. washwashed by EtOAc
  3. concentrationAfter concentration
  4. customthe crude product was purified by chromatography on a silica gel column

Sources & evidence

ORD record
ord-8d468e436d1241bb985beaf93d7bcbc9
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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