p-Toluenesulfonic acid → (2-(1-methyl-4-nitro-1H-pyrazol-5-yl)-1,3-dioxan-5-yl)methanol

HRID 521873

Reaction equation

HRID 521873 reaction equation
[CH3:1][N:2]1[C:6]([CH:7]=[O:8])=[C:5]([N+:9]([O-:11])=[O:10])[CH:4]=[N:3]1.[OH:12][CH2:13][CH:14]([CH2:17]O)[CH2:15][OH:16].C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[CH3:1][N:2]1[C:6]([CH:7]2[O:12][CH2:13][CH:14]([CH2:15][OH:16])[CH2:17][O:8]2)=[C:5]([N+:9]([O-:11])=[O:10])[CH:4]=[N:3]1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 78432TrimethylolmethaneHCID 598129402-Methyl-4-nitro-pyrazole-3-carbaldehyde2×

Product 1

HCID 86713821(2-(1-methyl-4-nitro-1H-pyrazol-5-yl)-1,3-dioxan-5-yl)methanol

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of 2-methyl-4-nitro-pyrazole-3-carbaldehyde (718 mg, 4.63 mmol, intermediate 3) in toluene (100 mL) was added 2-(hydroxymethyl)propane-1,3-diol (700 mg, 6.73 mmol) followed by p-toluenesulfonic acid (88 mg, 0.463 mmol). The reaction mixture was heated at reflux for 18 hr whilst azeotropically removing the water. The mixture was cooled to room temperature and concentrated under reduced pressure. The residue was diluted with DCM (50 mL) and washed with a saturated aqueous NaHCO3 (50 mL). The organic layer was washed with water (20 mL) and brine (20 mL), separated, dried over Na2SO4 and concentrated under reduced pressure. Purification via silica gel column chromatography (0-100% EtOAc/isohexane) gave (2-(1-methyl-4-nitro-1H-pyrazol-5-yl)-1,3-dioxan-5-yl)methanol (trans isomer) as the first eluting isomer as a colourless solid (220 mg, 20%). 1H NMR (400 MHz, CDCl3) δ 8.02 (s, 1H), 6.42 (s, 1H), 4.34 (dd, J=11.6, 4.7 Hz, 2H), 4.12 (s, 3H), 3.81 (t, J=11.5 Hz, 2H), 3.56 (t, J=5.1 Hz, 2H), 2.53-2.38 (m, 1H), 1.67 (t, J=4.6 Hz, 1H).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 18 hr
  3. customwhilst azeotropically removing the water
  4. concentrationconcentrated under reduced pressure
  5. additionThe residue was diluted with DCM (50 mL)
  6. washwashed with a saturated aqueous NaHCO3 (50 mL)
  7. washThe organic layer was washed with water (20 mL) and brine (20 mL)
  8. customseparated
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated under reduced pressure
  11. customPurification via silica gel column chromatography (0-100% EtOAc/isohexane)

Sources & evidence

ORD record
ord-8f2176cc1ef84bb0854f4fee4986bedc
Source dataset
uspto-grants-2016_05
Patent number
US09328106B2

Linked notes

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