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

HRID 2261753Notes

Reaction equation

HRID 2261753 reaction equation
CC(C)([O-])C.[K+].[Cl-].[CH3:8][O:9][CH2:10][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:50]=[CH:49][C:48]([C:51](=O)[CH3:52])=[C:47]([CH3:54])[CH:46]=2)=[C:41]([CH:55]([CH3:57])[CH3:56])[CH:40]=[N:39]1>C1COCC1>[Cl:37][C:33]1[CH:34]=[CH:35][CH:36]=[C:31]([Cl:30])[C:32]=1[N:38]1[C:42]([CH2:43][O:44][C:45]2[CH:50]=[CH:49][C:48]([C:51]([CH3:52])=[CH:8][O:9][CH3:10])=[C:47]([CH3:54])[CH:46]=2)=[C:41]([CH:55]([CH3:57])[CH3:56])[CH:40]=[N:39]1

Participants

5

Reactant 3

HCID 2723798Methoxymethyl-triphenylphosphonium chlorideHCID 23665647Potassium tert-butoxideHCID 574432701-{4-[2-(2,6-Dichloro-phenyl)-4-isopropyl-2H-pyrazol-3-ylmethoxy]-2-methyl-phenyl}-ethanone

Product 1

HCID 675282221-(2,6-Dichloro-phenyl)-4-isopropyl-5-[4-(2-methoxy-1-methyl-vinyl)-3-methyl-phenoxymethyl]-1H-pyrazoleYield 93%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a room temperature suspension of potassium tert-butoxide (1.36 g, 12.12 mmol) in THF (30 mL) is added (methoxymethyl)triphenyl phosphonium chloride (4.14 g, 12.12 mmol). The reaction mixture is stirred at room temperature for 20 minutes. Solid 1-{4-[2-(2,6-Dichloro-phenyl)-4-isopropyl-2H-pyrazol-3-ylmethoxy]-2-methyl-phenyl}-ethanone (843 mg, 2.02 mmol) is added and the reaction is stirred at room temperature overnight. The reaction is quenched with saturated aqueous NH4Cl and is concentrated under reduced pressure. 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 under reduced pressure, and chromatographed (0% to 30% EtOAc/Hex) to yield the title compound (836 mg, 93%) as a mix of E/Z isomers. (Major Isomer) 1H NMR (400 MHz, CDCl3) δ 7.70 (s, 1H), 7.41 (d, 2H, J=7.9 Hz), 7.33-7.28 (m, 1H), 6.93 (d, 1H, J=8.4 Hz), 6.64-6.52 (m, 2H), 5.83 (q, 1H, J=1.3 Hz), 4.78 (s, 2H), 3.63 (s, 3H), 3.00 (sept, 1H, J=7.0 Hz), 2.22 (s, 3H), 1.83 (d, 3H, J=1.3 Hz), 1.30 (d, 6H, J=7.0 Hz).

Workup

  1. stirringthe reaction is stirred at room temperature overnight
  2. customThe reaction is quenched with saturated aqueous NH4Cl
  3. concentrationis concentrated under reduced pressure
  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 under reduced pressure
  10. customchromatographed (0% to 30% EtOAc/Hex)

Sources & evidence

ORD record
ord-3142eaafb5e7413596d24e2950a382ce
Source dataset
uspto-grants-2010_12
Patent number
US07846960B2

Reaction notes

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