Sodium Hydroxide → 1-Amino-2-[4-(benzyloxy)phenyl]propan-2-ol

HRID 571767Notes

Reaction equation

HRID 571767 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15](=[O:17])[CH3:16])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Si]([C:22]#[N:23])(C)C.[H-].[H-].[H-].[H-].[Li+].[Al+3].[OH-].[Na+]>C1COCC1.[I-].[Zn+2].[I-].O>[NH2:23][CH2:22][C:15]([C:12]1[CH:13]=[CH:14][C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[CH:10][CH:11]=1)([OH:17])[CH3:16]

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 82115Trimethylsilyl cyanideHCID 2452261-[4-(Benzyloxy)phenyl]ethan-1-oneHCID 21226445Aluminium lithium hydride

Product 1

HCID 150366201-Amino-2-[4-(benzyloxy)phenyl]propan-2-olYield 86.2%

Reagents, catalysts & solvents 3

HCID 9883512zinc(II)iodideCatalystHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 1-(4-benzyloxy-phenyl)-ethanone (18.50 g; 81.8 mmol), zinc iodide (0.52 g; 1.6 mmol), and trimethylsilyl cyanide (33.8 mL; 269.8 mmol) was stirred overnight at RT. Subsequently, the excess trimethylsilyl cyanide was removed in vacuo, and the residue dissolved in THF (100 mL). The resulting solution was added, dropwise, to a mixture of LiAlH4 (12.7 g; 335.2 mmol) in THF (200 mL). The resulting mixture was heated under reflux for 2 h. Next, the mixture was cooled to 0° C. and treated successively with water (13 mL), 2M aqueous NaOH (26 mL), and water (13 mL). Thereafter the mixture was heated under reflux for 15 minutes, cooled again to RT, filtered over Kieselguhr, and concentrated in vacuo. The residue was purified by column chromatography (SiO2, MeOH) to afford 1-Amino-2-(4-benzyloxy-phenyl)-propan-2-ol (18.15 g).

Workup

  1. customSubsequently, the excess trimethylsilyl cyanide was removed in vacuo
  2. dissolutionthe residue dissolved in THF (100 mL)
  3. additionThe resulting solution was added
  4. temperatureThe resulting mixture was heated
  5. temperatureunder reflux for 2 h
  6. temperatureNext, the mixture was cooled to 0° C.
  7. temperatureThereafter the mixture was heated
  8. temperatureunder reflux for 15 minutes
  9. temperaturecooled again to RT
  10. filtrationfiltered over Kieselguhr
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by column chromatography (SiO2, MeOH)

Sources & evidence

ORD record
ord-e7cc158dabab40a5b91d9f418ce4aada
Source dataset
uspto-grants-2015_05
Patent number
US09029371B2

Reaction notes

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