Triethylamine → 1-[1-(4-Bromo-2,6-dimethylphenyl)-3,5-diethyl-1H-pyrazol-4-ylmethyl]-naphthalene-2-ol

HRID 1740108Notes

Reaction equation

HRID 1740108 reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[OH:11].[H-].[Na+].CS(Cl)(=O)=O.[Br:19][C:20]1[CH:25]=[C:24]([CH3:26])[C:23]([N:27]2[C:31]([CH2:32][CH3:33])=[C:30]([CH2:34]O)[C:29]([CH2:36][CH3:37])=[N:28]2)=[C:22]([CH3:38])[CH:21]=1.C(N(CC)CC)C.C1C=C2C(C=C([O-])C=C2)=CC=1.[Na+]>C(OCC)C>[Br:19][C:20]1[CH:21]=[C:22]([CH3:38])[C:23]([N:27]2[C:31]([CH2:32][CH3:33])=[C:30]([CH2:34][C:1]3[C:10]4[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=4)[CH:4]=[CH:3][C:2]=3[OH:11])[C:29]([CH2:36][CH3:37])=[N:28]2)=[C:24]([CH3:26])[CH:25]=1

Participants

8

Reactant 6

HCID 8471TriethylamineHCID 86632-NaphtholHCID 24758Sodium hydrideHCID 31297Methanesulfonyl chlorideHCID 218373201-(4-bromo-2,6-dimethylphenyl)-3,5-diethyl-1H-pyrazol-4-yl-methanolHCID 23664630Sodium 2-naphtholate

Product 1

HCID 537145601-[1-(4-Bromo-2,6-dimethylphenyl)-3,5-diethyl-1H-pyrazol-4-ylmethyl]-naphthalene-2-olYield 31.4%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

A solution of 2-naphthol (2.28 g, 15.8 mmol) in 20 ml of diethylether was treated with sodium hydride (60% mineral oil dispersion, 0.632 g, 15.8 mmol) and the mixture was stirred at ambient temperature for 20 minutes. Methanesulfonyl chloride (0.677 ml, 8.7 mmol) was added dropwise to an ice bath cooled solution of [1-(4-bromo-2,6-dimethyl-phenyl)-3,5-diethyl-1H-pyrazol-4-yl]-methanol (2.68 g, 7.9 mmol) and triethylamine (1.38 ml, 9.9 mmol) in diethylether (25 ml). The mixture was stirred at 0°-5° C. for 15 minutes; and then stirred at ambient temperature for 20 minutes. The mixture was then added to the above-described sodium 2-napthoxide suspension. After 16 hours stirring at ambient temperature, the reaction mixture was extracted with methylene chloride/dilute aqueous sodium bicarbonate (150 ml and 100 ml, respectively). The aqueous phase was extracted twice with 50 ml portions of methylene chloride. The combined organic extracts were dried over anhydrous sodium sulfate and concentrated in vacuo to an oil (5.65 g). Trituration of the entire sample with ethyl acetate/hexanes (5 ml and 45 ml, respectively) followed by filtration afforded the title compound 1.15 g as a colorless solid.

Workup

  1. stirringThe mixture was stirred at 0°-5° C. for 15 minutes
  2. stirringand then stirred at ambient temperature for 20 minutes
  3. stirringAfter 16 hours stirring at ambient temperature
  4. extractionthe reaction mixture was extracted with methylene chloride/dilute aqueous sodium bicarbonate (150 ml and 100 ml
  5. extractionThe aqueous phase was extracted twice with 50 ml portions of methylene chloride
  6. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
  7. concentrationconcentrated in vacuo to an oil (5.65 g)
  8. filtrationTrituration of the entire sample with ethyl acetate/hexanes (5 ml and 45 ml, respectively) followed by filtration

Sources & evidence

ORD record
ord-f2aa8f8000c043eba4933290721c522b
Source dataset
uspto-grants-1999_10
Patent number
US05968944

Reaction notes

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