Water → (Z)-1-[2-(benzyloxy)ethyl]-4-{4-[1,1,1,3,3,3-hexafluoro-2-(methoxymethoxy)propan-2-yl]-2-(prop-1-en-1-yl)phenyl}piperazine

HRID 1038524Notes

Reaction equation

HRID 1038524 reaction equation
[CH2:1]([O:8][CH2:9][CH2:10][N:11]1[CH2:16][CH2:15][N:14]([C:17]2[CH:22]=[CH:21][C:20]([C:23]([OH:32])([C:28]([F:31])([F:30])[F:29])[C:24]([F:27])([F:26])[F:25])=[CH:19][C:18]=2/[CH:33]=[CH:34]\[CH3:35])[CH2:13][CH2:12]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.Cl[CH2:46][O:47][CH3:48].O>ClCCl>[CH2:1]([O:8][CH2:9][CH2:10][N:11]1[CH2:16][CH2:15][N:14]([C:17]2[CH:22]=[CH:21][C:20]([C:23]([O:32][CH2:46][O:47][CH3:48])([C:28]([F:31])([F:30])[F:29])[C:24]([F:27])([F:25])[F:26])=[CH:19][C:18]=2/[CH:33]=[CH:34]\[CH3:35])[CH2:13][CH2:12]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 7864Chloromethyl Methyl Ether2×HCID 81531Diisopropylethylamine2×HCID 86647184(Z)-2-(4-{4-[2-(benzyloxy)ethyl]piperazin-1-yl}-3-(prop-1-en-1-yl)phenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol

Product 1

HCID 86647183(Z)-1-[2-(benzyloxy)ethyl]-4-{4-[1,1,1,3,3,3-hexafluoro-2-(methoxymethoxy)propan-2-yl]-2-(prop-1-en-1-yl)phenyl}piperazineYield 73.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(Z)-2-(4-{4-[2-(benzyloxy)ethyl]piperazin-1-yl}-3-(prop-1-en-1-yl)phenyl)-1,1,1,3,3,3-hexafluoropropan-2-ol (40 mg, 0.0796 mmol) was dried with a vacuum pump, and dissolved in dichloromethane (796 μL). Under ice-cold conditions, diisopropylethylamine (42 μL, 0.239 mmol) and chloromethylmethylether (6.6 μL, 0.0876 mmol) were added sequentially, and the mixture was stirred at room temperature for 20 hours. Further, under ice-cold conditions, diisopropylethylamine (84 μL, 0.478 mmol) and chloromethylmethylether (26 μL, 0.350 mmol) were added sequentially, and the mixture was stirred at room temperature overnight. The reaction solution was added water under ice-cold conditions, and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The obtained residue was purified by silica-gel column chromatography (hexane/acetone). The title compound (32 mg (yield 73%)) was obtained as a pale yellow oil.

Workup

  1. stirringthe mixture was stirred at room temperature overnight
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe obtained residue was purified by silica-gel column chromatography (hexane/acetone)

Sources & evidence

ORD record
ord-a9ce72af0c134d7da6c6af50258e8a6f
Source dataset
uspto-grants-2013_10
Patent number
US08551985B2

Reaction notes

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