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

HRID 408137Notes

Reaction equation

HRID 408137 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-9406489d06de4d0bbfbf9684dec3aece
Source dataset
uspto-grants-2014_06
Patent number
US08758830B2

Reaction notes

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