p-Toluenesulfonic acid → 1-(Oxan-2-yl)-1,2,4-triazole-3-carbonitrile

HRID 1398556Notes

Reaction equation

HRID 1398556 reaction equation
[NH:1]1[CH:5]=[N:4][C:3]([C:6]#[N:7])=[N:2]1.[O:8]1[CH:13]=[CH:12][CH2:11][CH2:10][CH2:9]1.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)(O)[O-].[Na+]>ClCCCl>[O:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[N:1]1[CH:5]=[N:4][C:3]([C:6]#[N:7])=[N:2]1

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 80803,4-dihydro-2H-pyranHCID 516892Sodium BicarbonateHCID 178510603HCID 178510603, compound

Product 1

HCID 214989441-(Oxan-2-yl)-1,2,4-triazole-3-carbonitrile

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of 1H-1,2,4-triazole-3-carbonitrile (1.00 g, 10.63 mmol) in DCE (10 mL) was added 3,4-dihydro-2H-pyran (1.94 ml, 21.26 mmol) and p-toluenesulfonic acid (183 mg, 1.06 mmol). The resulting mixture was stirred at room temperature under nitrogen for 15 minutes. Saturated aqueous sodium bicarbonate solution (25 mL) was added and the product extracted into DCM (25 mL×3). The combined organics were washed with brine (10 mL), dried (Na2SO4) and concentrated in vacuo. The crude product was purified by flash chromatography (Biotage, 0-10% methanol gradient in DCM) to give the title intermediate as a yellow oil: 1H NMR (500 MHz, CDCl3) delta 1.81-1.63 (3H, m), 2.11-1.95 (2H, m), 2.19 (1H, dd, J=8.1, 5.6 Hz), 3.87-3.65 (1H, m), 4.18-3.97 (1H, m), 5.53 (1H, dd, J=8.5, 2.9 Hz), 8.37 (1H, s).

Workup

  1. extractionthe product extracted into DCM (25 mL×3)
  2. washThe combined organics were washed with brine (10 mL)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by flash chromatography (Biotage, 0-10% methanol gradient in DCM)

Sources & evidence

ORD record
ord-9a9d3b21678d44409e65790559c55077
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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