Ammonium formate → methyl 5-[(2R)-2-aminopropyl]-1H-indole-2-carboxylate

HRID 1760717Notes

Reaction equation

HRID 1760717 reaction equation
C1([C@H]([NH:9][C@H:10]([CH3:25])[CH2:11][C:12]2[CH:13]=[C:14]3[C:18](=[CH:19][CH:20]=2)[NH:17][C:16]([C:21]([O:23][CH3:24])=[O:22])=[CH:15]3)C)C=CC=CC=1.C([O-])=O.[NH4+]>C(O)C.[OH-].[OH-].[Pd+2]>[NH2:9][C@H:10]([CH3:25])[CH2:11][C:12]1[CH:13]=[C:14]2[C:18](=[CH:19][CH:20]=1)[NH:17][C:16]([C:21]([O:23][CH3:24])=[O:22])=[CH:15]2

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 59979291Methyl 5-((2R)-2-{[(1R)-1-phenylethyl]amino]propyl)-1H-indole-2-carboxylate

Product 1

HCID 12988833methyl 5-[(2R)-2-aminopropyl]-1H-indole-2-carboxylateYield 107.6%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 702EthanolSolvent

Procedure

A solution of methyl 5-((2R)-2-{[(1R)-1-phenylethyl]amino}propyl)-1H-indole-2-carboxylate (Preparation 15, 9.34 g, 25.0 mmol) in ethanol (125 ml) was treated with ammonium formate (7.90 g, 125 mmol) and palladium hydroxide on carbon (2.81 g, 20% b/w palladium). The resulting suspension was purged with nitrogen and then heated to reflux for an hour. The reaction mixture was cooled to room temperature and filtered through arbocel to remove catalyst residues. The filtrate was reduced in vacuo and the residue was partitioned between 0.88 ammonia (100 ml) and dichloromethane (100 ml). The organic phase was separated and the aqueous extracted with more dichloromethane (100 ml). The combined organic extracts were dried (sodium sulphate) and the solvent removed in vacuo to give the title compound as a colourless oil (6.25 g, trace solvent remaining by 1H NMR).

Workup

  1. customThe resulting suspension was purged with nitrogen
  2. temperatureheated
  3. temperatureto reflux for an hour
  4. filtrationfiltered through arbocel
  5. customto remove catalyst residues
  6. customthe residue was partitioned between 0.88 ammonia (100 ml) and dichloromethane (100 ml)
  7. customThe organic phase was separated
  8. extractionthe aqueous extracted with more dichloromethane (100 ml)
  9. dry with materialThe combined organic extracts were dried (sodium sulphate)
  10. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-1ebdb16a2f934f489ab08c3c9832abc5
Source dataset
uspto-grants-2005_01
Patent number
US06844362B2

Reaction notes

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