Water → 3'-(4-Trifluoromethyl-phenyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazine

HRID 220425Notes

Reaction equation

HRID 220425 reaction equation
Cl[C:2]1[C:7]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=2)=[N:6][CH:5]=[CH:4][N:3]=1.Cl[C:19]1[C:24](C2C=CC(Cl)=CC=2)=[N:23][CH:22]=[CH:21][N:20]=1.N1CCNCC1.O>C(Cl)Cl>[F:15][C:14]([F:17])([F:16])[C:11]1[CH:12]=[CH:13][C:8]([C:7]2[C:2]([N:20]3[CH2:21][CH2:22][NH:23][CH2:24][CH2:19]3)=[N:3][CH:4]=[CH:5][N:6]=2)=[CH:9][CH:10]=1

Participants

6

Reactant 4

HCID 962WaterHCID 4837PiperazineHCID 131998892-Chloro-3-(4-chlorophenyl)pyrazineHCID 656455182-Chloro-3-(4-trifluoromethylphenyl)-pyrazine2×

Product 1

HCID 685948383'-(4-Trifluoromethyl-phenyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Prepare 2-chloro-3-(4-trifluoromethylphenyl)-pyrazine in 30% according to the procedure used to make 2-chloro-3-(4-chlorophenyl)-pyrazine. Couple 2-chloro-3-(4-trifluoromethylphenyl)-pyrazine (0.570 g, 2.20 mmol) and piperazine (4.31 g, 50.0 mmol), at 125° C. for 111 min. Cool the reaction to about 70° C., add water (50 mL), stir until the reaction temperature is below 35° C. and dilute with DCM (70 mL). Separate the layers, extract the aqueous layer with DCM (2×70 mL), wash the combined organic layers with saturated aqueous sodium chloride, dry (magnesium sulfate), concentrate and purify (silica gel chromatography, eluting with 0:100 to 1:1 ethyl acetate:hexanes), to give the title preparation (0.384 g, 57%). MS (ES): m/z=309 [M+H]+.

Workup

  1. temperatureCool
  2. customthe reaction to about 70° C.
  3. customis below 35° C.
  4. customSeparate the layers
  5. extractionextract the aqueous layer with DCM (2×70 mL)
  6. washwash the combined organic layers with saturated aqueous sodium chloride
  7. dry with materialdry (magnesium sulfate)
  8. concentrationconcentrate
  9. custompurify
  10. wash(silica gel chromatography, eluting with 0:100 to 1:1 ethyl acetate:hexanes)
  11. customto give the title
  12. custompreparation (0.384 g, 57%)

Sources & evidence

ORD record
ord-29880e8cc25447a285e1bf5147b5b193
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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