Benzyl chloroformate → cis-Tert-butyl 3-(benzyloxycarbonylamino)-4-fluoropiperidine-1-carboxylate

HRID 1923665Notes

Reaction equation

HRID 1923665 reaction equation
[N:1]([C@H:4]1[C@@H:9]([F:10])[CH2:8][CH2:7][N:6]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:5]1)=[N+]=[N-].[C:18](Cl)(=[O:27])[O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>CO.N1C=CC=CC=1.[Pd]>[CH2:20]([O:19][C:18]([NH:1][C@H:4]1[C@@H:9]([F:10])[CH2:8][CH2:7][N:6]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:5]1)=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

6

Reactant 2

HCID 10387Benzyl chloroformateHCID 131729718cis-Tert-butyl 3-azido-4-fluoropiperidine-1-carboxylate

Product 1

HCID 131729719cis-Tert-butyl 3-(benzyloxycarbonylamino)-4-fluoropiperidine-1-carboxylateYield 22%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 1049PyridineSolvent

Procedure

A mixture of cis-tert-butyl 3-azido-4-fluoropiperidine-1-carboxylate (1.40 g, 5.73 mmol) and 10% Pd/C (0.61 g, 0.57 mmol) in MeOH (20 mL) was charged 1 atmosphere H2 and stirred at room temperature for 1 hour. The catalyst was removed by filtration and washed with methanol. The filtrate was concentrated in vacuo. The residue obtained was dissolved in pyridine (10 mL) and benzyl carbonochloridate (1.61 mL, 11.46 mmol) was added. The reaction was stirred at room temperature for 2 hours. The pyridine was removed in vacuo, and the residue was dissolved in ethyl acetate (30 mL), washed with brine, dried (sodium sulfate) and concentrated in vacuo. The residue obtained was purified by flash chromatography on silica gel (hexane:ethyl acetate 3:1) to give cis-tert-butyl 3-(benzyloxycarbonylamino)-4-fluoropiperidine-1-carboxylate (0.44 g, 22%) as a solid.

Workup

  1. additionwas charged 1 atmosphere H2
  2. customThe catalyst was removed by filtration
  3. washwashed with methanol
  4. concentrationThe filtrate was concentrated in vacuo
  5. customThe residue obtained
  6. stirringThe reaction was stirred at room temperature for 2 hours
  7. customThe pyridine was removed in vacuo
  8. dissolutionthe residue was dissolved in ethyl acetate (30 mL)
  9. washwashed with brine
  10. dry with materialdried (sodium sulfate)
  11. concentrationconcentrated in vacuo
  12. customThe residue obtained
  13. customwas purified by flash chromatography on silica gel (hexane:ethyl acetate 3:1)

Sources & evidence

ORD record
ord-3963e67f5998428c8d180ad5e00f79e4
Source dataset
uspto-grants-2012_05
Patent number
US08178131B2

Reaction notes

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