Diethyl Ether → cis-Tert-butyl 3-azido-4-fluoropiperidine-1-carboxylate

HRID 2203703Notes

Reaction equation

HRID 2203703 reaction equation
[F:1][C@@H:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][C@H:3]1OS(C1C=CC(C)=CC=1)(=O)=O.[N-:26]=[N+:27]=[N-:28].[Na+].CCOCC>CN(C=O)C>[N:26]([C@H:3]1[C@@H:2]([F:1])[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4]1)=[N+:27]=[N-:28]

Participants

5

Reactant 3

HCID 3283Diethyl EtherHCID 33557Sodium AzideHCID 131729717trans-Tert-butyl 4-fluoro-3-(tosyloxy)piperidine-1-carboxylate

Product 1

HCID 131729718cis-Tert-butyl 3-azido-4-fluoropiperidine-1-carboxylateYield 54.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
128 °C

Procedure

A mixture of trans-tert-butyl 4-fluoro-3-(tosyloxy)piperidine-1-carboxylate (3.95 g, 10.6 mmol) and NaN3 (1.72 g, 26.4 mmol) in DMF (30 mL) was stirred at 128° C. (bath) for 18 hours. After cooling to room temperature, ether (100 mL) was added. The mixture was washed with brine (2×50 mL), dried (sodium sulfate) and concentrated in vacuo. The residue obtained was purified by flash chromatography on silica gel (hexane:ethyl acetate 4:1) to give cis-tert-butyl 3-azido-4-fluoropiperidine-1-carboxylate (1.40 g, 54%).

Workup

  1. temperatureAfter cooling to room temperature
  2. washThe mixture was washed with brine (2×50 mL)
  3. dry with materialdried (sodium sulfate)
  4. concentrationconcentrated in vacuo
  5. customThe residue obtained
  6. customwas purified by flash chromatography on silica gel (hexane:ethyl acetate 4:1)

Sources & evidence

ORD record
ord-38a8c0a9fb2b479fa2d041109c7256b0
Source dataset
uspto-grants-2016_06
Patent number
US09365568B2

Reaction notes

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