Methoxymethyl-triphenylphosphonium chloride → 1-(2,6-dichloro-phenyl)-4-isopropyl-5-[4-(2-methoxy-vinyl)-3-methyl-phenoxymethyl]-1H-pyrazole

HRID 2261757Notes

Reaction equation

HRID 2261757 reaction equation
[CH3:1][C:2](C)([O-:4])C.[K+].[Cl-].[CH3:8]OC[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cl:30][C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([Cl:37])[C:32]=1[N:38]1[C:42]([CH2:43][O:44][C:45]2[CH:52]=[CH:51][C:48](C=O)=[C:47]([CH3:53])[CH:46]=2)=[C:41]([CH:54]([CH3:56])[CH3:55])[CH:40]=[N:39]1>C1COCC1>[Cl:30][C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([Cl:37])[C:32]=1[N:38]1[C:42]([CH2:43][O:44][C:45]2[CH:52]=[CH:51][C:48]([CH:1]=[CH:2][O:4][CH3:8])=[C:47]([CH3:53])[CH:46]=2)=[C:41]([CH:54]([CH3:55])[CH3:56])[CH:40]=[N:39]1

Participants

5

Reactant 3

HCID 2723798Methoxymethyl-triphenylphosphonium chlorideHCID 23665647Potassium tert-butoxideHCID 866354624-[2-(2,6-Dichloro-phenyl)-4-isopropyl-2H-pyrazol-3-ylmethoxy]-2-methyl-benzaldehyde

Product 1

HCID 675279671-(2,6-dichloro-phenyl)-4-isopropyl-5-[4-(2-methoxy-vinyl)-3-methyl-phenoxymethyl]-1H-pyrazoleYield 73%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To an ambient temperature suspension of potassium tert-butoxide (668 mg, 5.96 mmol) in THF (20 mL) is added (methoxymethyl)triphenyl phosphonium chloride (2.04 g, 5.96 mmol) and is stirred at room temperature for 20 min. Solid 4-[2-(2,6-Dichloro-phenyl)-4-isopropyl-2H-pyrazol-3-ylmethoxy]-2-methyl-benzaldehyde (400 mg, 0.992 mmol) is added and the reaction is stirred at room temperature overnight. The reaction is quenched with sat. aq. NH4Cl and concentrated. The residue is partitioned between Et2O and water. The aqueous layer is extracted with Et2O and the combined organic layers are washed with brine, dried (MgSO4), filtered, concentrated and chromatographed (SiO2 120 g, 0% to 30% EtOAC/Hex) to yield the title compound (302 mg, 73%) as a mix of E/Z isomers. 1H NMR (400 MHz, CDCl3) (major isomer) δ 7.70 (s, 1H), 7.43-7.38 (m, 2H), 7.33-7.26 (m, 1H), 7.08 (d, 1H, J=8.4 Hz), 6.72 (d, 1H, J=12.8 Hz), 6.60-6.52 (m, 2H), 5.82 (d, 1H, J=12.8 Hz), 4.78 (s, 2H), 3.66 (s, 3H), 3.00 (sept, 1H, J=7.0 Hz), 2.22 (s, 3H), 1.30 (d, 6H, J=7.0 Hz).

Workup

  1. stirringthe reaction is stirred at room temperature overnight
  2. customThe reaction is quenched with sat. aq. NH4Cl
  3. concentrationconcentrated
  4. customThe residue is partitioned between Et2O and water
  5. extractionThe aqueous layer is extracted with Et2O
  6. washthe combined organic layers are washed with brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customchromatographed (SiO2 120 g, 0% to 30% EtOAC/Hex)

Sources & evidence

ORD record
ord-4f485ba2f0bb4e0e9d4e85aab549bc5a
Source dataset
uspto-grants-2010_12
Patent number
US07846960B2

Reaction notes

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