Hydrogen Bromide → HCID 59392821, compound

HRID 216717Notes

Reaction equation

HRID 216717 reaction equation
[CH2:1]([N:3]1[CH2:8][CH2:7][N:6]([C:9]2[CH:14]=[CH:13][C:12](N)=[CH:11][C:10]=2[CH3:16])[CH2:5][CH2:4]1)[CH3:2].[BrH:17].N([O-])=O.[Na+]>O.[Cu]Br>[Br:17][C:12]1[CH:13]=[CH:14][C:9]([N:6]2[CH2:7][CH2:8][N:3]([CH2:1][CH3:2])[CH2:4][CH2:5]2)=[C:10]([CH3:16])[CH:11]=1

Participants

6

Reactant 3

HCID 260Hydrogen Bromide2×HCID 2118783882147-67-3HCID 23668193Sodium Nitrite

Product 1

HCID 59392821HCID 59392821, compound

Reagents, catalysts & solvents 2

HCID 24593copper(I) bromideCatalystHCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

4-(4-Ethyl-piperazin-1-yl)-3-methyl-phenylamine (1.3 g, 6 mmol) in hydrobromic acid (61% in H2O, 9.2 ml, 70 mmol) is diazotized at 0° C. with sodium nitrite (443 mg, 6.42 mmol) in 2.3 ml H2O and the mixture is poured into a solution of copper(I) bromide (1.84 g, 12.5 mmol) in hydrobromic acid (61% in H2O, 7.7 ml, 58.8 mmol) at 0° C. The cooling bath is then removed and the mixture is heated at 60° C. for 5 h. After cooling, the mixture is basified with a 2M NaOH solution and diluted with CH2Cl2. After separation, the aqueous phase is extracted with CH2Cl2 several times. The combined organic layers are washed with brine, dried over Na2SO4, filtered and the filtrate is concentrated in vacuo. The residue is purified by chromatography on a 120 g silica gel column on a Combiflash Companion™ (Isco Inc.) apparatus (gradient CH2Cl2/CH2Cl2:EtOH:NH3 90:9:1 from 1:0=>4:6) to afford the title compound as a pale brown solid, Rt=0.878 min (Acquity HPLC BEH C18, 2.1×50 mm, 1.7 micron, detection 215 nM, 0.1 min 2% CH3CN in H2O, 2% to 100% CH3CN in H2O in 1.5 min, 0.4 min 100% CH3CN+0.1% TFA, flow rate 1.0 ml/min); MS: 283 (M+1, 79Br)+.

Workup

  1. customThe cooling bath is then removed
  2. temperatureAfter cooling
  3. additiondiluted with CH2Cl2
  4. customAfter separation
  5. extractionthe aqueous phase is extracted with CH2Cl2 several times
  6. washThe combined organic layers are washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationthe filtrate is concentrated in vacuo
  10. customThe residue is purified by chromatography on a 120 g silica gel column on a Combiflash Companion™ (Isco Inc.) apparatus (gradient CH2Cl2/CH2Cl2:EtOH:NH3 90:9:1 from 1:0=>4:6)

Sources & evidence

ORD record
ord-b02f9022c02a4107acfe806e4c274022
Source dataset
uspto-grants-2012_06
Patent number
US08193189B2

Reaction notes

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