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

HRID 2202275Notes

Reaction equation

HRID 2202275 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]1[CH:34]=[CH:33][C:8]([CH2:9][N:10]([CH2:24][C:25]2[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=2)[C:11]2[CH:16]=[C:15]([F:17])[C:14]([C:18]([CH3:22])([CH3:21])[CH2:19][OH:20])=[C:13]([F:23])[CH:12]=2)=[CH:7][CH:6]=1.I[CH2:36][CH3:37].[Cl-].[NH4+]>CN(C=O)C>[CH2:36]([O:20][CH2:19][C:18]([C:14]1[C:13]([F:23])=[CH:12][C:11]([N:10]([CH2:9][C:8]2[CH:7]=[CH:6][C:5]([O:4][CH3:3])=[CH:34][CH:33]=2)[CH2:24][C:25]2[CH:26]=[CH:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=2)=[CH:16][C:15]=1[F:17])([CH3:22])[CH3:21])[CH3:37]

Participants

6

Reactant 4

HCID 6340IodoethaneHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 118622795HCID 118622795, compound

Product 1

HCID 1186227154-(1-ethoxy-2-methylpropan-2-yl)-3,5-difluoro-N,N-bis(4-methoxybenzyl)anilineYield 105%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (60%, oil, 1.726 g, 43.15 mmol) was added to a solution of 2-(4-(bis(4-methoxybenzyl)amino)-2,6-difluorophenyl)-2-methylpropan-1-ol (7.62 g, 17.26 mmol) and iodoethane (3.49 mL, 43.15 mmol) in DMF (30 mL) at 5° C., and the mixture was stirred at room temperature for 14 hr. To the reaction mixture was added aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate (×2). 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 (Diol, solvent gradient; 5→20% ethyl acetate/hexane) to give 4-(1-ethoxy-2-methylpropan-2-yl)-3,5-difluoro-N,N-bis(4-methoxybenzyl)aniline (8.51 g, 18.12 mmol, 105%) as a colorless oil.

Workup

  1. extractionthe mixture was extracted with ethyl acetate (×2)
  2. washThe organic layer was washed with brine
  3. dry with materialdried over magnesium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe obtained residue was purified by silica gel column chromatography (Diol, solvent gradient; 5→20% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-80189d29ebe14e2c8fabd5002261615e
Source dataset
uspto-grants-2016_06
Patent number
US09365520B2

Reaction notes

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