Dimethylformamide → trans-(+)-3-Azido-4-(4-chloro-3-fluorophenoxy)-1-methylpyrrolidine

HRID 2279604Notes

Reaction equation

HRID 2279604 reaction equation
CS(O[C@H:6]1[C@@H:10]([O:11][C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([F:19])[CH:13]=2)[CH2:9][N:8]([CH3:20])[CH2:7]1)(=O)=O.CN(C=O)C.[N-:26]=[N+:27]=[N-:28].[Na+]>O>[N:26]([C@H:6]1[C@H:10]([O:11][C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([F:19])[CH:13]=2)[CH2:9][N:8]([CH3:20])[CH2:7]1)=[N+:27]=[N-:28]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 33557Sodium AzideHCID 86705586cis-(+/-)-4-(4-Chloro-3-fluorophenoxy)-1-methylpyrrolidin-3-yl methanesulfonate

Product 1

HCID 86705585trans-(+)-3-Azido-4-(4-chloro-3-fluorophenoxy)-1-methylpyrrolidineYield 89.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 424 (400 mg, 1.24 mmol) and DMF (2.0 mL) was added sodium azide (0.806 g, 12.4 mmol). The mixture was heated at 90° C. overnight. The mixture was cooled, diluted with H2O (30 mL) and extracted with EtOAc (3×50 mL). The combined extracts were washed with water (3×30 mL), dried (Na2SO4), filtered and concentrated in vacuo to afford 300 mg of trans-(±)-3-azido-4-(4-chloro-3-fluorophenoxy)-1-methylpyrrolidine (426) which was used for next step without further purification: LC-MS (ESI) m/z 271 (M+H).

Workup

  1. temperatureThe mixture was cooled
  2. extractionextracted with EtOAc (3×50 mL)
  3. washThe combined extracts were washed with water (3×30 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c787f2dd20c140e791a8c9baa8644098
Source dataset
uspto-grants-2015_09
Patent number
US09133187B2

Reaction notes

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