Tert-butyl cis-4-azido-3-fluoro-piperidine-1-carboxylate → 1,1-Dimethylethyl (3R,4S)-4-amino-3-fluoro-1-piperidinecarboxylate

HRID 1095728Notes

Reaction equation

HRID 1095728 reaction equation
[N:1]([C@H:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][C@H:5]1[F:17])=[N+]=[N-]>[Pd].C1COCC1.CCO>[NH2:1][C@H:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:15])([CH3:14])[CH3:16])=[O:11])[CH2:6][C@H:5]1[F:17]

Participants

5

Reactant 1

HCID 121592108Tert-butyl cis-4-azido-3-fluoro-piperidine-1-carboxylate

Product 1

HCID 112644351,1-Dimethylethyl (3R,4S)-4-amino-3-fluoro-1-piperidinecarboxylateYield 35.7%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Palladium on carbon (10%, 0.876 g, 0.823 mmol) was added to a solution of (cis)-tert-butyl 4-azido-3-fluoropiperidine-1-carboxylate (2.01 g, 8.23 mmol) dissolved in THF and EtOH (1:1, 82 mL). The reaction was placed under a hydrogen atmosphere (balloon pressure) and stirred for 2 hours. The mixture was filtered through GF/F paper and concentrated in vacuo. The amine was purified on a Varian Bond Elut SCX column, eluting with methylene chloride followed by a solution of MeOH containing 6% aqueous NH4OH. The second eluant was concentrated in vacuo to provide the desired product (642 mg). MS ESI (+) m/z 218.8 (M+1) detected.

Workup

  1. filtrationThe mixture was filtered through GF/F paper
  2. concentrationconcentrated in vacuo
  3. customThe amine was purified on a Varian Bond Elut SCX column
  4. washeluting with methylene chloride
  5. concentrationThe second eluant was concentrated in vacuo

Sources & evidence

ORD record
ord-6448526351fd41b691e4edf377c1ca96
Source dataset
uspto-grants-2012_03
Patent number
US08138181B2

Reaction notes

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