Ammonium Chloride → HCID 67327486, compound

HRID 1023334Notes

Reaction equation

HRID 1023334 reaction equation
Br[C:2]1[CH:21]=[CH:20][C:5]([CH2:6][N:7]2[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]2)=[C:4]([F:22])[CH:3]=1.[Li]CCCC.[NH4+].[Cl-].[BH4-].[Na+].[C:32]([O-])(O)=[O:33].[Na+]>CO.CN(C=O)C.C1COCC1>[F:22][C:4]1[CH:3]=[C:2]([CH2:32][OH:33])[CH:21]=[CH:20][C:5]=1[CH2:6][N:7]1[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]1

Participants

9

Reactant 5

HCID 25517Ammonium ChlorideHCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 67328284HCID 67328284, compoundHCID 178418339Butyllithium

Product 1

HCID 67327486HCID 67327486, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a THF (44 mL) solution of tert-butyl 4-(4-bromo-2-fluorobenzyl)piperazine-1-carboxylate (8.445 g) was added slowly n-BuLi (11.31 mL, 2.6 M in hexane) at −78° C., then the resultant mixture was stirred for 0.5 hour. To the mixture was added slowly DMF (1.927 mL) at −78° C. After stirring for 1 hour at −78° C., then the mixture was stirred at room temperature over night. The mixture was poured into saturated aqueous NH4Cl, and extracted with AcOEt. The organic layer was washed with water and saturated aqueous NaCl, dried over anhydrous Na2SO4, and evaporated. The residue was purified by silica gel column chromatography (n-hexane/AcOEt=9/1 to 2/1) to afford a colorless oil. To a MeOH (13 mL) solution of that colorless oil was added NaBH4 (0.200 g) at 0° C., then the resultant mixture was stirred for 5 hours. To the reaction mixture was added saturated aqueous NaHCO3, and extracted with AcOEt. The organic layer was washed with saturated aqueous NaCl, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane/AcOEt=3/1 to 1/1) to afford tert-butyl 4-[2-fluoro-4-(hydroxymethyl)benzyl]piperazine-1-carboxylate as a colorless oil (0.500 g).

Workup

  1. stirringthe mixture was stirred at room temperature over night
  2. extractionextracted with AcOEt
  3. washThe organic layer was washed with water and saturated aqueous NaCl
  4. dry with materialdried over anhydrous Na2SO4
  5. customevaporated
  6. customThe residue was purified by silica gel column chromatography (n-hexane/AcOEt=9/1 to 2/1)
  7. customto afford a colorless oil
  8. extractionextracted with AcOEt
  9. washThe organic layer was washed with saturated aqueous NaCl
  10. dry with materialdried over anhydrous Na2SO4
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by silica gel column chromatography (n-hexane/AcOEt=3/1 to 1/1)

Sources & evidence

ORD record
ord-7a161faedc9c4571b17c19dbd8620e15
Source dataset
uspto-grants-2014_05
Patent number
US08722663B2

Reaction notes

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