Ammonium Chloride → (S)-1-Azido-2-(5-bromo-2-fluoro-phenyl)-propan-2-ol

HRID 81574Notes

Reaction equation

HRID 81574 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:12])=[C:6]([C@@:8]2([CH3:11])[CH2:10][O:9]2)[CH:7]=1.[N-:13]=[N+:14]=[N-:15].[Na+].[NH4+].[Cl-].C1OCCOCCOCCOCCOCCOC1>CCO>[N:13]([CH2:10][C@:8]([C:6]1[CH:7]=[C:2]([Br:1])[CH:3]=[CH:4][C:5]=1[F:12])([OH:9])[CH3:11])=[N+:14]=[N-:15]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 2855718-Crown-6HCID 33557Sodium AzideHCID 86650263(S)-2-(5-Bromo-2-fluoro-phenyl)-2-methyl-oxirane

Product 1

HCID 86650264(S)-1-Azido-2-(5-bromo-2-fluoro-phenyl)-propan-2-ol

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of (S)-2-(5-bromo-2-fluoro-phenyl)-2-methyl-oxirane (51.85 g, 224 mmol) in EtOH (800 ml) was added NaN3 (36.8 g, 531 mmol), NH4Cl (60.6 g, 1122 mmol) and 18-crown-6 (59.8 g, 224 mmol) and the reaction mixture was heated at reflux for 6 h. The reaction mixture was filtered and concentrated to half of its volume. The residual oil was extracted with EtOAc. Combined extracts were washed with saturated NaHCO3 solution and brine, dried over MgSO4, filtered and concentrated to provide the title compound as a light yellow oil: TLC (hexane-EtOAc 1:1): Rf=0.70; HPLC RtH3=1.115 min; 1H NMR (360 MHz, CDCl3): δ 7.72 (dd, 1H), 7.32 (m, 1H), 6.85 (dd, 1H), 3.73 (d, 1H), 3.51 (d, 1H), 2.44 (s, 1H), 1.50 (s, 3H).

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux for 6 h
  3. filtrationThe reaction mixture was filtered
  4. concentrationconcentrated to half of its volume
  5. extractionThe residual oil was extracted with EtOAc
  6. washCombined extracts were washed with saturated NaHCO3 solution and brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-228fb833022e43cf98be5b13ff4da600
Source dataset
uspto-grants-2014_09
Patent number
US08846658B2

Reaction notes

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