Triethylamine → trans-2-[4-(6-Trifluoromethyl-benzo[b]thiophen-3-yl)-piperazin-1-ylmethyl]-cyclopropanecarboxylic Acid Methyl Ester

HRID 2111689Notes

Reaction equation

HRID 2111689 reaction equation
[F:1][C:2]([F:19])([F:18])[C:3]1[CH:4]=[CH:5][C:6]2[C:10]([N:11]3[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]3)=[CH:9][S:8][C:7]=2[CH:17]=1.[CH3:20][O:21][C:22]([C@@H:24]1[CH2:26][C@H:25]1[CH2:27]OS(C)(=O)=O)=[O:23].C(N(CC)CC)C>C(#N)C>[CH3:20][O:21][C:22]([C@@H:24]1[CH2:26][C@H:25]1[CH2:27][N:14]1[CH2:13][CH2:12][N:11]([C:10]2[C:6]3[CH:5]=[CH:4][C:3]([C:2]([F:18])([F:1])[F:19])=[CH:17][C:7]=3[S:8][CH:9]=2)[CH2:16][CH2:15]1)=[O:23]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 112891551-(6-Trifluoromethyl-benzo[b]thiophen-3-yl)-piperazineHCID 86591119trans-2-Methanesulfonyloxymethyl-cyclopropanecarboxylic acid methyl ester

Product 1

HCID 68456225trans-2-[4-(6-Trifluoromethyl-benzo[b]thiophen-3-yl)-piperazin-1-ylmethyl]-cyclopropanecarboxylic Acid Methyl Ester

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Heat at reflux for 16 h, a mixture of 1-(6-trifluoromethyl-benzo[b]thiophen-3-yl)-piperazine, free base of Example 2b, (23.0 g, 71.3 mmol), trans-2-methanesulfonyloxymethyl-cyclopropanecarboxylic acid methyl ester (Example 5a) (15.3 g, 73.5 mmol), and triethylamine (40 mL, 288 mmol) in acetonitrile (600 mL). Concentrate the reaction mixture under reduced pressure and dilute the resultant oil with EtOAc (30 mL). Filter the resulting precipitate (unreacted starting piperazine) away and purify the filtrate by column chromatography over silica gel (EtOAc/heptane/MeOH/triethylamine, 20:20:1). Concentration of the appropriate fractions gives 18.0 g of colorless oil, m/z=413 (M+H)+.

Workup

  1. temperatureHeat
  2. temperatureat reflux for 16 h
  3. concentrationConcentrate the reaction mixture under reduced pressure
  4. additiondilute the resultant oil with EtOAc (30 mL)
  5. filtrationFilter the resulting precipitate (unreacted starting piperazine) away
  6. custompurify the filtrate by column chromatography over silica gel (EtOAc/heptane/MeOH/triethylamine, 20:20:1)

Sources & evidence

ORD record
ord-4dc1c0082dfa4b5198af96fe86f67c0c
Source dataset
uspto-grants-2009_04
Patent number
US07521445B2

Reaction notes

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