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

HRID 521872

Reaction equation

HRID 521872 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.[CH2:12]([C:14]([CH2:19]O)([CH2:17][OH:18])[CH2:15][OH:16])[CH3:13].C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[CH2:12]([C:14]1([CH2:17][OH:18])[CH2:15][O:16][CH:7]([C:6]2[N:2]([CH3:1])[N:3]=[CH:4][C:5]=2[N+:9]([O-:11])=[O:10])[O:8][CH2:19]1)[CH3:13]

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 6510TrimethylolpropaneHCID 598129402-Methyl-4-nitro-pyrazole-3-carbaldehyde2×

Product 1

HCID 86713820(5-ethyl-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 (370 mg, 2.39 mmol, intermediate 3) in toluene (50 mL) was added 2-ethyl-2-(hydroxymethyl)propane-1,3-diol (315 mg, 2.35 mmol) followed by p-toluenesulfonic acid (20 mg, 0.10 mmol). The reaction mixture was heated at reflux for 36 hr whilst azeotropically removing the water. The mixture was cooled to room temperature and concentrated under reduced pressure. Purification via silica gel column chromatography (0-100% EtOAc/isohexane) gave (5-ethyl-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 (244 mg, 38%). 1H NMR (400 MHz, CDCl3) δ 8.02 (s, 1H), 6.38 (s, 1H), 4.16 (s, 3H), 4.02 (d, J=11.5 Hz, 2H), 3.97 (d, J=5.2 Hz, 2H), 3.42 (d, J=3.8 Hz, 2H), 1.90 (m, 3H), 0.99 (t, J=7.6 Hz, 3H).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 36 hr
  3. customwhilst azeotropically removing the water
  4. concentrationconcentrated under reduced pressure
  5. customPurification via silica gel column chromatography (0-100% EtOAc/isohexane)

Sources & evidence

ORD record
ord-336fc74a336b40bca70b3094d68a10ee
Source dataset
uspto-grants-2016_05
Patent number
US09328106B2

Linked notes

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