Sodium hydride → 1-Chloro-4-(4-methoxy-benzyloxymethyl)-2-trifluoromethyl-benzene

HRID 1828701Notes

Reaction equation

HRID 1828701 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][OH:9])=[CH:4][C:3]=1[C:10]([F:13])([F:12])[F:11].[H-].[Na+].[CH3:16][O:17][C:18]1[CH:25]=[CH:24][C:21]([CH2:22]Br)=[CH:20][CH:19]=1>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][O:9][CH2:22][C:21]2[CH:24]=[CH:25][C:18]([O:17][CH3:16])=[CH:19][CH:20]=2)=[CH:4][C:3]=1[C:10]([F:11])([F:12])[F:13]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 1650214-Methoxybenzyl bromideHCID 27781114-Chloro-3-(trifluoromethyl)benzyl alcohol

Product 1

HCID 220577531-Chloro-4-(4-methoxy-benzyloxymethyl)-2-trifluoromethyl-benzene

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of crude (4-chloro-3-trifluoromethyl-phenyl)-methanol in DMF (anhydrous, 40 mL) at 0° C. is added NaH (600 mg, 15 mmol). After stirring for 30 min, 4-methoxy benzylbromide (2.21 g, 11 mmol) is added dropwise via syringe. After stirring at room temperature for 3 h, the reaction is quenched by pouring into a mixture of ice and saturated aqueous NH4Cl. The mixture is extracted with EtOAc (3×30 mL), and the combined organic layers are washed with saturated aqueous NaCl and dried over Na2SO4. After concentration, the crude product is purified by silica gel chromatography (5% EtOAc in hexanes) to give 1-chloro-4-(4-methoxy-benzyloxymethyl)-2-trifluoromethyl-benzene as a colorless oil.

Workup

  1. stirringAfter stirring at room temperature for 3 h
  2. customthe reaction is quenched
  3. additionby pouring into a mixture of ice and saturated aqueous NH4Cl
  4. extractionThe mixture is extracted with EtOAc (3×30 mL)
  5. washthe combined organic layers are washed with saturated aqueous NaCl
  6. dry with materialdried over Na2SO4
  7. concentrationAfter concentration
  8. customthe crude product is purified by silica gel chromatography (5% EtOAc in hexanes)

Sources & evidence

ORD record
ord-0ea43b5e8df84a4ea99b57514f7cf29a
Source dataset
uspto-grants-2006_06
Patent number
US07060697B2

Reaction notes

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