Reaction #1121814

ord-42c48422998643bba463b58348699956

Reaction equation

Cc1ccc(S(=O)(=O)O[C@@H]2CN(C(=O)OC(C)(C)C)CC[C@H]2F)cc1
trans-tert-butyl 4-fluoro-3-(tosyloxy)piperidine-1-carboxylate
[N-]=[N+]=[N-].[Na+]
NaN3
CCOCC
ether
→
CC(C)(C)OC(=O)N1CC[C@H](F)[C@H](N=[N+]=[N-])C1
cis-tert-butyl 3-azido-4-fluoropiperidine-1-carboxylate
Yield 54.1%

Reactants

Cc1ccc(S(=O)(=O)O[C@@H]2CN(C(=O)OC(C)(C)C)CC[C@H]2F)cc1
trans-tert-butyl 4-fluoro-3-(tosyloxy)piperidine-1-carboxylate
[N-]=[N+]=[N-].[Na+]
NaN3
CCOCC
ether

Reagents

None

Solvents

CN(C)C=O
DMF

Conditions

Temperature
128°CELSIUS
Detailed conditions
See reaction.notes.procedure_details.

Workup

  1. 1
    TemperatureAfter cooling to room temperature
  2. 2
    WashThe mixture was washed with brine (2×50 mL)
  3. 3
    Dryingdried (sodium sulfate)
  4. 4
    Concentrationconcentrated in vacuo
  5. 5
    OtherThe residue obtained
  6. 6
    Otherwas purified by flash chromatography on silica gel (hexane:ethyl acetate 4:1)

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%).

Source

DOI: 10.6084/m9.figshare.5104873.v1Patent: US08545897B2uspto-grants-2013_10