Ethanol → Tert-butyl 4-azido-5-hydroxyazepane-1-carboxylate

HRID 1244355Notes

Reaction equation

HRID 1244355 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:15][CH2:14][CH:13]2[CH:11]([O:12]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(O)C.[Cl-].[NH4+].[N-:21]=[N+:22]=[N-:23].[Na+]>O>[C:1]([O:5][C:6]([N:8]1[CH2:15][CH2:14][CH:13]([OH:12])[CH:11]([N:21]=[N+:22]=[N-:23])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 702EthanolHCID 25517Ammonium ChlorideHCID 33557Sodium AzideHCID 58717040Tert-butyl 8-oxa-4-azabicyclo[5.1.0]octane-4-carboxylate

Product 1

HCID 58717042Tert-butyl 4-azido-5-hydroxyazepane-1-carboxylateYield 79%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
75 °C

Procedure

To a stirred solution of 16.4 g 2,3,6,7-tetrahydro-azepine-1-carboxylic acid tert-butyl ester in 420 ml dichloromethane was added at −60° C. 35.8 g m-chloroperbenzoic acid (70% purity). The mixture was allowed to slowly warm to room temperature overnight, 1 l ethylacetate was added and the solution was extracted with aqueous sodium bicarbonate, 1N aqueous sodium hydroxide and brine. Evaporation of the solvent and chromatography yielded 14.5 g (82%) 8-oxa-4-aza-bicyclo[5.1.0]octane-4-carboxylic acid tert-butyl ester as colorless liquid; MS (EI): m/e=213 (M+,5%), 158 (22%), 140 (12%), 57 (100%). To a solution of 14.3 g 8-oxa-4-aza-bicyclo[5.1.0]octane-4-carboxylic acid tert-butyl ester in 750 ethanol was added 150 ml water, 35.8 g ammonium chloride and 43.6 g sodium azide. The mixture was stirred at 75° C. over night, the solvents were greatly removed by distillation under vacuum and the residue was suspended in ethanol and filtered. The ethanol was distilled off and the residue was suspended in ethylacetate and filtered. Removal of the solvent and chromatography on silicagel with ethylacetate/hexane 1:1, yielded 13.5 g (79%) 4-azido-5-hydroxy-azepane-1-carboxylic acid tert-butyl ester as a viscous oil; MS (ISP): m/e=257 (M+H+).

Workup

  1. customthe solvents were greatly removed by distillation under vacuum
  2. filtrationfiltered
  3. distillationThe ethanol was distilled off
  4. filtrationfiltered
  5. customRemoval of the solvent and chromatography on silicagel with ethylacetate/hexane 1:1

Sources & evidence

ORD record
ord-d233336c2a784dcd9dc7e50315b802eb
Source dataset
uspto-grants-2006_10
Patent number
US07122545B2

Reaction notes

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