Sodium hydride → tert-Butyl 4-(2-((4-chloro-5-iodo-2-methoxyphenyl)amino)ethyl)piperazine-1-carboxylate

HRID 588850Notes

Reaction equation

HRID 588850 reaction equation
[Cl:1][C:2]1[C:8]([I:9])=[CH:7][C:5]([NH2:6])=[C:4]([O:10][CH3:11])[CH:3]=1.[H-].[Na+].[C:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][N:24]([CH2:27][CH2:28]Br)[CH2:23][CH2:22]1)=[O:20])([CH3:17])([CH3:16])[CH3:15]>C1COCC1>[Cl:1][C:2]1[C:8]([I:9])=[CH:7][C:5]([NH:6][CH2:28][CH2:27][N:24]2[CH2:25][CH2:26][N:21]([C:19]([O:18][C:14]([CH3:15])([CH3:17])[CH3:16])=[O:20])[CH2:22][CH2:23]2)=[C:4]([O:10][CH3:11])[CH:3]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 15946441tert-Butyl 4-(2-bromoethyl)piperazine-1-carboxylateHCID 917583774-Chloro-5-iodo-2-methoxyaniline

Product 1

HCID 90464834tert-Butyl 4-(2-((4-chloro-5-iodo-2-methoxyphenyl)amino)ethyl)piperazine-1-carboxylateYield 21.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 4-chloro-5-iodo-2-methoxyaniline (968 mg, 3.42 mmol) in anhydrous THF (20 mL) at 0° C., NaH (60% in mineral oil, 205.2 mg, 5.13 mmol) was added and the resulting mixture was stirred at reflux under nitrogen for 1 h. To this mixture, tert-butyl-4-(2-bromoethyl)piperazine-1-carboxylate (500 mg, 1.71 mmol) was added and the resulting mixture was stirred at room temperature for 15 h. The mixture was concentrated in vacuo and the residue was partitioned between ethyl acetate and brine. The organic layer was dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (10-30% ethyl acetate/petroleum ether) to afford the desired product (180 mg, 21% yield) as a solid.

Workup

  1. temperatureat reflux under nitrogen for 1 h
  2. stirringthe resulting mixture was stirred at room temperature for 15 h
  3. concentrationThe mixture was concentrated in vacuo
  4. customthe residue was partitioned between ethyl acetate and brine
  5. dry with materialThe organic layer was dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash column chromatography on silica gel (10-30% ethyl acetate/petroleum ether)

Sources & evidence

ORD record
ord-628ecf50f66444ea9eb36e969f36f18e
Source dataset
uspto-grants-2016_01
Patent number
US09227978B2

Reaction notes

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