Hydrochloric Acid → HCID 9167299, compound

HRID 2119355Notes

Reaction equation

HRID 2119355 reaction equation
[NH:1]1[CH2:7][CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.Cl.CCO.Cl.Br[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]#[N:22])=[CH:17][CH:16]=1>CCO>[C:21]([C:18]1[CH:19]=[CH:20][C:15]([CH2:14][N:1]2[CH2:7][CH2:6][CH2:5][NH:4][CH2:3][CH2:2]2)=[CH:16][CH:17]=1)#[N:22]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 68163Hexahydro-1,4-diazepineHCID 869964-(Bromomethyl)benzonitrileHCID 21887872Ethanol hydrochloride

Product 1

HCID 9167299HCID 9167299, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of homopiperazine (9.2 g, 92 mmol, 2 equiv). in EtOH (115 mL) was added 1 M HCl-EtOH (92 mL) dropwise over 1 h. The suspension was heated to 70° C. for 1 h at which point a homogeneous solution of monohydrochloride salt was obtained. α-Bromo-p-tolunitrile (9.0 g, 46 mnmol, 1 equiv) was added and the reaction mixture was heated to reflux for 5 h. After cooling, the solvent was removed by rotary evaporation and the residue was partitioned between CH2Cl2 (100 mL) and 2N aqueous KOH (100 mL). The aqueous layer was extracted with CH2Cl2 (5×50 mL) and the combined organic phase was washed with saturated aqueous NaCl (1×150 mL) and dried (MgSO4). Chromatography (SiO2, 4×20 cm, 20% CH3OH —5% Et3N—CH2Cl2) afforded the desired monoalkylated material (6.78 g, 10.1 g theoretical, 67%) as an amber oil.

Workup

  1. customwas obtained
  2. temperaturethe reaction mixture was heated
  3. temperatureto reflux for 5 h
  4. temperatureAfter cooling
  5. customthe solvent was removed by rotary evaporation
  6. customthe residue was partitioned between CH2Cl2 (100 mL) and 2N aqueous KOH (100 mL)
  7. extractionThe aqueous layer was extracted with CH2Cl2 (5×50 mL)
  8. washthe combined organic phase was washed with saturated aqueous NaCl (1×150 mL)
  9. dry with materialdried (MgSO4)
  10. customChromatography (SiO2, 4×20 cm, 20% CH3OH —5% Et3N—CH2Cl2) afforded the desired monoalkylated material (6.78 g, 10.1 g theoretical, 67%) as an amber oil

Sources & evidence

ORD record
ord-9cc9bbaba619437f83c52ec490707827
Source dataset
uspto-grants-2004_02
Patent number
US06686353B1

Reaction notes

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