Benzene → 6-Chloro-2-(4-cyclopropylmethyl-1-piperazinyl)-pyrazine hydrochloride

HRID 261066Notes

Reaction equation

HRID 261066 reaction equation
C1C=CC=CC=1.Cl.[Cl:8][C:9]1[N:14]=[C:13]([N:15]2[CH2:20][CH2:19][N:18]([C:21]([CH:23]3[CH2:25][CH2:24]3)=O)[CH2:17][CH2:16]2)[CH:12]=[N:11][CH:10]=1>CCOCC.C(O)C.C(O)(C)C>[ClH:8].[Cl:8][C:9]1[N:14]=[C:13]([N:15]2[CH2:20][CH2:19][N:18]([CH2:21][CH:23]3[CH2:24][CH2:25]3)[CH2:17][CH2:16]2)[CH:12]=[N:11][CH:10]=1

Participants

6

Reactant 3

HCID 241BenzeneHCID 313Hydrochloric Acid2×HCID 203960016-Chloro-2-(4-cyclopropanecarbonyl-1-piperazinyl)-pyrazine

Product 1

HCID 203960146-Chloro-2-(4-cyclopropylmethyl-1-piperazinyl)-pyrazine hydrochloride

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 22179027Isopropanol ethanolSolvent

Procedure

To a stirred slurry of 3.0 g (11 mmol) of the product from the previous step in 30 ml dry ether is added 5.5 ml of a 70% benzene solution of sodium bis-2-methoxyethoxyaluminum hydride at -20° C. under N2. The temperature of the mixture is raised to +10° C. for 20 minutes and the mixture is recooled to -20° C. and treated dropwise with 33 ml 4 N aqueous hydrochloric acid. The aqueous acid layer is extracted with chloroform, adjusted to pH8 with sodium bicarbonate and the crude title base extracted with chloroform and chromatographed on silica gel. Elution with ethylacetatechloroform gives fractions containing 0.8 g (29%) of pure title base which is converted to the hydrochloride, mp 254° C. dec in ethanol-isopropanol containing hydrochloric acid.

Workup

  1. temperatureThe temperature of the mixture is raised to +10° C. for 20 minutes
  2. customis recooled to -20° C.
  3. extractionThe aqueous acid layer is extracted with chloroform
  4. extractionthe crude title base extracted with chloroform
  5. customchromatographed on silica gel
  6. washElution with ethylacetatechloroform
  7. customgives fractions

Sources & evidence

ORD record
ord-475abd387ef8447196e09d27c3cb3083
Source dataset
uspto-grants-1979_08
Patent number
US04163849

Reaction notes

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