Water → 4-Amino-4-(4-chlorophenyl)butan-1-ol

HRID 423073Notes

Reaction equation

HRID 423073 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[N:14]OC)[CH2:9][CH2:10][C:11](O)=[O:12])=[CH:4][CH:3]=1.B.O1CCCC1.O>O1CCCC1>[NH2:14][CH:8]([C:5]1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=1)[CH2:9][CH2:10][CH2:11][OH:12]

Participants

5

Reactant 3

HCID 962WaterHCID 2723981Borane;tetrahydrofuranHCID 866320534-(4-Chlorophenyl)-4-(methoxyimino)butanoic acid2×

Product 1

HCID 577503714-Amino-4-(4-chlorophenyl)butan-1-olYield 73%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

4-(4-Chlorophenyl)-4-(methoxyimino)butanoic acid (Intermediate 53) (6.43 g, 26.61 mmol) in tetrahydrofuran (30 mL) was cooled, under an atmosphere of nitrogen, in an ice-methanol bath. Borane-tetrahydrofuran complex (1.0M in THF) (93 mL, 93.12 mmol) was added dropwise over a period of 20 minutes. The resulting solution was allowed to warm to room temperature, stirred for 1 hour then heated at reflux for a further 6 hours. After cooling in ice-water the mixture was treated with water (20 mL) dropwise with stirring over 10 minutes. The mixture was again allowed to warm to room temperature and stirred for 2 hours before evaporating the bulk of the solvent. The residue was then cooled in ice-water and 50% NaOH (aq.) (20 mL) added dropwise with stirring. The resulting mixture was stirred and heated at 90° C. for 4 hours then cooled to room temperature and extracted three times with Et2O. The combined extracts were washed with water followed by brine, dried over MgSO4 and evaporated to dryness. The crude product was then purified by flash silica chromatography (eluent 0-10% 7N ammonia in MeOH/DCM) and pure fractions evaporated to afford 4-amino-4-(4-chlorophenyl)butan-1-ol (3.88 g, 73.0%) as a colourless, transparent gum.

Workup

  1. temperaturethen heated
  2. temperatureat reflux for a further 6 hours
  3. stirringwith stirring over 10 minutes
  4. temperatureto warm to room temperature
  5. stirringstirred for 2 hours
  6. custombefore evaporating the bulk of the solvent
  7. temperatureThe residue was then cooled in ice-water
  8. addition50% NaOH (aq.) (20 mL) added dropwise
  9. stirringwith stirring
  10. stirringThe resulting mixture was stirred
  11. temperatureheated at 90° C. for 4 hours
  12. temperaturethen cooled to room temperature
  13. extractionextracted three times with Et2O
  14. washThe combined extracts were washed with water
  15. dry with materialdried over MgSO4
  16. customevaporated to dryness
  17. customThe crude product was then purified by flash silica chromatography (eluent 0-10% 7N ammonia in MeOH/DCM) and pure fractions
  18. customevaporated

Sources & evidence

ORD record
ord-38756436a1ae414892a36f6184c361e7
Source dataset
uspto-grants-2012_01
Patent number
US08101623B2

Reaction notes

Loading…