Borane → 4-Pyrazol-1-YL-benzylamine

HRID 241287Notes

Reaction equation

HRID 241287 reaction equation
[N:1]1([C:6]2[CH:13]=[CH:12][C:9]([C:10]#[N:11])=[CH:8][CH:7]=2)[CH:5]=[CH:4][CH:3]=[N:2]1.B.O1CCCC1>CO>[N:1]1([C:6]2[CH:13]=[CH:12][C:9]([CH2:10][NH2:11])=[CH:8][CH:7]=2)[CH:5]=[CH:4][CH:3]=[N:2]1

Participants

5

Reactant 3

HCID 6331BoraneHCID 8028TetrahydrofuranHCID 120796294-(1-Pyrazolyl)benzonitrile

Product 1

HCID 27764834-Pyrazol-1-YL-benzylamineYield 83%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To 4-(pyrazol-1-yl)benzonitrile (see WO 2005/095343A) (1.46 g, 8.63 mmol) was added a solution of 1M borane.tetrahydrofuran complex in tetrahydrofuran (93 ml, 93 mmol), followed by heating to reflux for 16 hours. After completion of the reaction, methanol (14 ml) was added to the reaction solution, followed by concentration under reduced pressure. 6N Hydrochloric acid (265 ml) was added to the residue, followed by further heating to reflux for 3 hours. After this solution was concentrated under reduced pressure, a small amount of water was added. The resulting solution was adjusted to pH 11 with a 30% aqueous sodium hydroxide solution under ice cooling, followed by extraction with methylene chloride. The separated organic layer was dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography (eluent; chloroform:methanol:28% aqueous ammonia=90:10:1 (V/V/V)), and fractions containing the desired compound were concentrated under reduced pressure to afford the title compound (1.24 g) as a pale yellow solid. (Yield: 83%)

Workup

  1. temperatureby heating
  2. temperatureto reflux for 16 hours
  3. additionwas added to the reaction solution
  4. concentrationfollowed by concentration under reduced pressure
  5. addition6N Hydrochloric acid (265 ml) was added to the residue
  6. temperatureby further heating
  7. temperatureto reflux for 3 hours
  8. concentrationAfter this solution was concentrated under reduced pressure
  9. additiona small amount of water was added
  10. extractionfollowed by extraction with methylene chloride
  11. dry with materialThe separated organic layer was dried over anhydrous sodium sulfate
  12. concentrationconcentrated under reduced pressure
  13. additioncontaining the desired compound
  14. concentrationwere concentrated under reduced pressure

Sources & evidence

ORD record
ord-079be0120139403dae437cdbc8f107dc
Source dataset
uspto-grants-2014_02
Patent number
US08648097B2

Reaction notes

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