Methyl (S)-3-(5-aminopyridin-2-yl)-2-((tert-butoxycarbonyl)amino)propanoate → tert-butyl(2S)-6-amino-3-oxooctahydroindolizin-2-ylcarbamate

HRID 919632Notes

Reaction equation

HRID 919632 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C@H:9]([NH:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[C:10](OC)=[O:11])=[N:6][CH:7]=1>CC(O)=O.[Rh]>[NH2:1][CH:2]1[CH2:3][CH2:4][CH:5]2[N:6]([C:10](=[O:11])[C@@H:9]([NH:14][C:15](=[O:16])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:8]2)[CH2:7]1

Participants

4

Reactant 1

HCID 117891709Methyl (S)-3-(5-aminopyridin-2-yl)-2-((tert-butoxycarbonyl)amino)propanoate

Product 1

HCID 68070552tert-butyl(2S)-6-amino-3-oxooctahydroindolizin-2-ylcarbamateYield 103.7%

Reagents, catalysts & solvents 2

HCID 23948RhodiumCatalystHCID 176Acetic AcidSolvent

Procedure

A solution of (S)-methyl 3-(5-aminopyridin-2-yl)-2-(tert-butoxycarbonylamino)propanoate (0.965 g, 3.27 mmol) 127.1 (prepared as described in WO2002068393) in glacial AcOH (40 mL) was treated with 5% Rh/C (0.67 g) and stirred at room temperature under a 60 psi H2 atmosphere for 25 hr. The catalyst was removed by filtration through a celite pad, rinsing with MeOH. The filtrate was concentrated to dryness and azeotroped from toluene (2×). The residue was dissolved in MeOH (50 mL) and treated with polymer-supported carbonate resin (2.5 g, 3.5 mmole/g) and stirred at room temperature for 24 hr. The resin was removed by filtration and the filtrate concentrated in vacuo to afford of tert-butyl (2S)-6-amino-3-oxooctahydroindolizin-2-ylcarbamate (0.913 g) 127.2 as a clear viscous oil that was used without further purification. LCMS (ESI) m/z: 270.2 [M+H]+.

Workup

  1. customThe catalyst was removed by filtration through a celite pad
  2. washrinsing with MeOH
  3. concentrationThe filtrate was concentrated to dryness
  4. customazeotroped from toluene (2×)
  5. dissolutionThe residue was dissolved in MeOH (50 mL)
  6. additiontreated with polymer-supported carbonate resin (2.5 g, 3.5 mmole/g)
  7. stirringstirred at room temperature for 24 hr
  8. customThe resin was removed by filtration
  9. concentrationthe filtrate concentrated in vacuo

Sources & evidence

ORD record
ord-5fa5470eec8b4bc28af209ac5091bf75
Source dataset
uspto-grants-2016_03
Patent number
US09273028B2

Reaction notes

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