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

HRID 991672Notes

Reaction equation

HRID 991672 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-1-(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 CHCl3/H2O. The aqueous phase was made alkaline and extracted with CHCl3 (×3). Tie 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 CHCl3/H2O
  8. extractionextracted with CHCl3 (×3)
  9. dry with materialwere dried (MgSO4)
  10. customthe solvent was evaporated
  11. customThe resulting oil was purified by column chromatography on silica

Sources & evidence

ORD record
ord-23333118a9e844f6a940a5286ec120c3
Source dataset
uspto-grants-2002_10
Patent number
US06465467B1

Reaction notes

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