1-Chloroethyl chloroformate → 1-(3-Chloro-2-pyrazinyl)-2-ethylpiperazine, Hydrochloride

HRID 493328Notes

Reaction equation

HRID 493328 reaction equation
[Cl:1]C(OC(Cl)C)=O.C([N:15]1[CH2:20][CH2:19][N:18]([C:21]2[C:26]([Cl:27])=[N:25][CH:24]=[CH:23][N:22]=2)[CH:17]([CH2:28][CH3:29])[CH2:16]1)C1C=CC=CC=1>C(Cl)Cl>[ClH:1].[Cl:27][C:26]1[C:21]([N:18]2[CH2:19][CH2:20][NH:15][CH2:16][CH:17]2[CH2:28][CH3:29])=[N:22][CH:23]=[CH:24][N:25]=1

Participants

4

Reactant 2

HCID 5213051-Chloroethyl chloroformateHCID 220363902-Chloro-3-[2-ethyl-4-(phenylmethyl)-1-piperazinyl]pyrazine

Product 1

HCID 1317235541-(3-Chloro-2-pyrazinyl)-2-ethylpiperazine, Hydrochloride

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1-Chloroethyl chloroformate (2.11 g, 15.2 mmol) was added with a syringe during 1 h to an ice cold (˜0° C.) solution of 4-benzyl-l,-(3-chloro-2-pyrazinyl)-2-ethylpiperazine (3.22 g, 10.1 mmol, from Step 2) in dry CH2Cl2 (30 mL). The reaction was allowed to slowly reach room temperature and stirred for 48 h. The solvent was evaporated from the reaction mixture and MeOH was added to the resulting oil. The mixture was heated to reflux for 2 h, the solvent was evaporated and the resulting oil was partitioned between CHC13/H2O. The aqueous phase was made alkaline and extracted with CHCl3 (×3). The combined organic phases were dried (MgSO4), and the solvent was evaporated. The resulting oil was purified by column chromatography on silica using CHCl3/MeOH/NH4OH (95:5:0.2) as eluent to give a quantitative yield (2.35 g) of the free base of the title compound as a slightly yellow oil. An analytical sample was prepared as its hydrochloric acid salt (from HCl/ether): mp 195-197° C. Anal. (C10H15ClN4.HCl) C, H, N.

Workup

  1. customwas allowed to slowly reach room temperature
  2. customThe solvent was evaporated from the reaction mixture and MeOH
  3. additionwas added to the resulting oil
  4. temperatureThe mixture was heated
  5. temperatureto reflux for 2 h
  6. customthe solvent was evaporated
  7. customthe resulting oil was partitioned between CHC13/H2O
  8. extractionextracted with CHCl3 (×3)
  9. dry with materialThe combined organic phases were dried (MgSO4)
  10. customthe solvent was evaporated
  11. customThe resulting oil was purified by column chromatography on silica

Sources & evidence

ORD record
ord-c6ef8529f42241649bf276aa47548673
Source dataset
uspto-grants-2009_05
Patent number
US07534794B2

Reaction notes

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