Ammonium Chloride → Racemic (2R,5S,6S)-5-Azido-6-hydroxy-2-methyl-azepane-1-carboxylic acid benzyl ester

HRID 229795Notes

Reaction equation

HRID 229795 reaction equation
[N-:1]=[N+:2]=[N-:3].[Na+].[CH2:5]([O:12][C:13]([N:15]1[CH:22]([CH3:23])[CH2:21][CH2:20][CH:19]2[CH:17]([O:18]2)[CH2:16]1)=[O:14])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[Cl-].[NH4+]>CO.O>[CH2:5]([O:12][C:13]([N:15]1[CH2:16][CH:17]([OH:18])[CH:19]([N:1]=[N+:2]=[N-:3])[CH2:20][CH2:21][CH:22]1[CH3:23])=[O:14])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 33557Sodium AzideHCID 21036429racemic (1S,4R,7R)-4-methyl-8-oxa-3-aza-bicyclo[5.1.0]octane-3-carboxylic acid benzyl ester

Product 1

HCID 21036431Racemic (2R,5S,6S)-5-Azido-6-hydroxy-2-methyl-azepane-1-carboxylic acid benzyl esterYield 80.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

Sodium azide (0.56 g, 8.62 mmol) was added to a solution of racemic (1S,4R,7R)-4-methyl-8-oxa-3-aza-bicyclo[5.1.0]octane-3-carboxylic acid benzyl ester (0.75 g, 2.87 mmol) and ammonium chloride (0.46 g, 8.62 mmol) in MeOH (5 ml) and H2O (0.5 ml), then was refluxed for 6 h. The reaction mixture was concentrated in vacuo by rotary evaporation, then was diluted with water (5 ml) and extracted with EtOAc (10 ml). The organic layer was then extracted with water, brine, dried with MgSO4, filtered, concentrated in vacuo by rotary evaporation, and chromatographed (silica gel, 20% EtOAc/hexanes) to yield the title compound (0.7 g, 80%): 7.39-7.30 (m, 5H), 5.15 (2H, s), 4.10-3.67 (m, 2H), 3.10 (1H, d), 1.85-1.53 (m, 4H), 1.09 (3H, d); Liquid Chromatgraphy/Electrospray mass spec: M+H+=305.2.

Workup

  1. temperaturewas refluxed for 6 h
  2. concentrationThe reaction mixture was concentrated in vacuo by rotary evaporation
  3. additionwas diluted with water (5 ml)
  4. extractionextracted with EtOAc (10 ml)
  5. extractionThe organic layer was then extracted with water, brine
  6. dry with materialdried with MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo by rotary evaporation
  9. customchromatographed (silica gel, 20% EtOAc/hexanes)

Sources & evidence

ORD record
ord-6acd4caa76d14639852c52959f336148
Source dataset
uspto-grants-2009_07
Patent number
US07563784B2

Reaction notes

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