Water → 3,5-difluoro-4-(1-methoxy-2-methylpropan-2-yl)-N,N-bis(4-methoxybenzyl)aniline

HRID 2202317Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:32]=[CH:31][C:6]([CH2:7][N:8]([CH2:22][C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2)[C:9]2[CH:14]=[C:13]([F:15])[C:12]([C:16]([CH3:20])([CH3:19])[CH2:17][OH:18])=[C:11]([F:21])[CH:10]=2)=[CH:5][CH:4]=1.I[CH3:34].[H-].[Na+].O>CN(C=O)C>[F:21][C:11]1[CH:10]=[C:9]([CH:14]=[C:13]([F:15])[C:12]=1[C:16]([CH3:20])([CH3:19])[CH2:17][O:18][CH3:34])[N:8]([CH2:7][C:6]1[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:32][CH:31]=1)[CH2:22][C:23]1[CH:24]=[CH:25][C:26]([O:29][CH3:30])=[CH:27][CH:28]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 2-(4-(bis(4-methoxybenzyl)amino)-2,6-difluorophenyl)-2-methylpropan-1-ol (1.31 g, 2.97 mmol) and iodomethane (0.278 mL, 4.45 mmol) in DMF (10 mL) was added sodium hydride (60%, oil, 0.154 g, 3.86 mmol) at 0° C., and the mixture was stirred at 0° C. for 4 hr. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (solvent gradient; 3→40% ethyl acetate/hexane) to give 3,5-difluoro-4-(1-methoxy-2-methylpropan-2-yl)-N,N-bis(4-methoxybenzyl)aniline (1.000 g, 2.195 mmol, 74.0%) a yellow oil.

Workup

extractionthe mixture was extracted with ethyl acetate
washThe organic layer was washed with brine
dry with materialdried over magnesium sulfate
customthe solvent was evaporated under reduced pressure
customThe obtained residue was purified by silica gel column chromatography (solvent gradient; 3→40% ethyl acetate/hexane)

Sources & evidence

ORD record: ord-98fc9486206c4ed4a62ffdd4251c5ab9
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09365520B2

Reaction notes

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