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

HRID 2100658Notes

Reaction equation

[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][OH:7])=[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]Cl)=[CH:20][CH:19]=1.[NH4+].[Cl-]>CN(C=O)C>[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][O:7][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

Conditions

Temperature: 0 °C

Procedure

To a solution of 4-chloro-3-(trifluoromethyl)benzyl alcohol (2.87 g, 13.63 mmol) in DMF (40 mL) is added sodium hydride (60% in mineral oil, 654 mg, 16.36 mmol) at 0° C. and the reaction mixture is stirred at 0° C. for 30 minutes. 4-methoxy-benzyl chloride (2.35 g, 15 mmol) in DMF (10 mL) is added and the reaction mixture is stirred at 0° C. for 1 h and at room temperature for 3 hours. The reaction mixture is poured into saturated aqueous NH4Cl (300 mL) and extracted with EtOAc. The combined extracts are washed with brine (2×80 mL) and dried over Na2SO4. After concentration, the residue is purified by silica gel chromatography (8:1 hexanes/EtOAc) to give 1-Chloro-4-(4-methoxy-benzyloxymethyl)-2-trifluoromethyl-benzene.

Workup

stirringthe reaction mixture is stirred at 0° C. for 1 h and at room temperature for 3 hours
extractionextracted with EtOAc
washThe combined extracts are washed with brine (2×80 mL)
dry with materialdried over Na2SO4
concentrationAfter concentration
customthe residue is purified by silica gel chromatography (8:1 hexanes/EtOAc)

Sources & evidence

ORD record: ord-91eda08a73cb4937b07670b4544480cd
Source dataset: uspto-grants-2009_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07572811B2

Reaction notes

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