Sodium Azide → [5-(5-Azido-2-fluoro-phenyl)-5-difluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl ester

HRID 81546Notes

Reaction equation

HRID 81546 reaction equation
[C:1]([O:5][C:6](=[O:25])[NH:7][C:8]1[CH2:9][O:10][CH2:11][C:12]([C:17]2[CH:22]=[C:21](Br)[CH:20]=[CH:19][C:18]=2[F:24])([CH:14]([F:16])[F:15])[N:13]=1)([CH3:4])([CH3:3])[CH3:2].CN[C@@H]1CCCC[C@H]1NC.[N-:36]=[N+:37]=[N-:38].[Na+].O=C1O[C@H]([C@H](CO)O)C([O-])=C1O.[Na+]>CCO.O.CC(OC)(C)C.[Cu]I>[C:1]([O:5][C:6](=[O:25])[NH:7][C:8]1[CH2:9][O:10][CH2:11][C:12]([C:17]2[CH:22]=[C:21]([N:36]=[N+:37]=[N-:38])[CH:20]=[CH:19][C:18]=2[F:24])([CH:14]([F:16])[F:15])[N:13]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 4

HCID 33557Sodium AzideHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 23667548Sodium AscorbateHCID 66665878HCID 66665878, compound

Product 1

HCID 86650258[5-(5-Azido-2-fluoro-phenyl)-5-difluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 7.27 g (17.18 mmol) [5-(5-bromo-2-fluoro-phenyl)-5-difluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl ester and 2.443 g (17.18 mmol) trans-N,N′-dimethylcyclohexane-1,2-diamine in 237 ml EtOH was added a solution of 8.93 g (137 mmol) sodium azide and 1.361 g (6.87 mmol) sodium-ascorbate in 102 ml water. The mixture was degassed and brought under nitrogen atmosphere. CuI (1.309 g, 6.87 mmol) was added and the mixture was heated at 70° C. The initially formed suspension turned into a homogeneous blue solution. The mixture was cooled to rt, diluted with water and TBME. The organic phase was washed with brine and dried with MgSO4.H2O. The crude product was purified by chromatography on silica gel (hexane/5-8% TBME) to give the desired product as a colorless solid.

Workup

  1. customThe mixture was degassed
  2. temperatureThe mixture was cooled to rt
  3. washThe organic phase was washed with brine
  4. dry with materialdried with MgSO4.H2O
  5. customThe crude product was purified by chromatography on silica gel (hexane/5-8% TBME)

Sources & evidence

ORD record
ord-edaaecf1ed4043e2b4c32d50a88fac0a
Source dataset
uspto-grants-2014_09
Patent number
US08846658B2

Reaction notes

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