Ammonium Chloride → HCID 22393825, compound

HRID 1071637Notes

Reaction equation

HRID 1071637 reaction equation
CC(C)([O-])C.[K+].[OH:7][CH2:8][CH2:9][N:10]1[CH2:15][CH2:14][N:13](C(OCC2C=CC=CC=2)=O)[CH2:12][CH2:11]1.F[C:27]1[CH:34]=[CH:33][C:32]([F:35])=[CH:31][C:28]=1[C:29]#[N:30].[Cl-].[NH4+]>CO.[C].[Pd].C(OCC)C.O1CCCC1>[C:29]([C:28]1[CH:31]=[C:32]([F:35])[CH:33]=[CH:34][C:27]=1[O:7][CH2:8][CH2:9][N:10]1[CH2:11][CH2:12][NH:13][CH2:14][CH2:15]1)#[N:30]

Participants

9

Reactant 4

HCID 25517Ammonium ChlorideHCID 1235582,5-DifluorobenzonitrileHCID 22393803Benzyl 4-(2-hydroxyethyl)piperazine-1-carboxylateHCID 23665647Potassium tert-butoxide

Product 1

HCID 22393825HCID 22393825, compoundYield 80%

Reagents, catalysts & solvents 4

HCID 178418390HCID 178418390, compoundCatalystHCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Under nitrogen atmosphere, potassium tert-butoxide (869 mg) was added to a tetrahydrofuran solution (10 ml) of benzyl 4-(2-hydroxyethyl)-1-piperazinecarboxylate (1.86 g) in an ice bath. After stirring for one hour, the reaction system was transferred to a dry ice-methanol bath, and after 10 minutes, a 2,5-difluorobenzonitrile (1.09 g)/tetrahydrofuran solution (5 ml) was added thereto. After stirring for 2 hours while the temperature of the reaction system was naturally returned to a room temperature, an aqueous saturated ammonium chloride and diethyl ether were added thereto, to separate the organic layer. The resulting organic layer was washed with water and brine, and dried over anhydrous magnesium sulfate. After filtering off the drying agent, the filtrate was evaporated. The residue was purified by silica gel column chromatography (hexane:ethyl acetate system), to give a colorless oil as an intermediate (1.10 g, 46%). The intermediate (1.10 g) was dissolved in methanol (10 mL), 10% palladium carbon (100 mg) was added, and the mixture was stirred at room temperature under hydrogen atmosphere. After 1.5 hours, the reaction catalyst was filtered through Celite, and the filtrate was evaporated. The resulting title compound (647 mg, 80%) obtained was used for the next reaction as it was.

Workup

  1. customthe reaction system was transferred to a dry ice-methanol bath
  2. waitafter 10 minutes
  3. stirringAfter stirring for 2 hours while the temperature of the reaction system
  4. customwas naturally returned to a room temperature
  5. customto separate the organic layer
  6. washThe resulting organic layer was washed with water and brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationAfter filtering off the drying agent
  9. customthe filtrate was evaporated
  10. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate system)
  11. customto give a colorless oil as an intermediate (1.10 g, 46%)
  12. stirringthe mixture was stirred at room temperature under hydrogen atmosphere
  13. waitAfter 1.5 hours
  14. filtrationthe reaction catalyst was filtered through Celite
  15. customthe filtrate was evaporated

Sources & evidence

ORD record
ord-ca62558c0276465e91ee2db7757c19a7
Source dataset
uspto-grants-2005_06
Patent number
US06906072B1

Reaction notes

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