Benzyl Alcohol → rel-1-(tert-butyl) 3-methyl (3R,5S)-5-aminopiperidine-1,3-dicarboxylate

HRID 2192771Notes

Reaction equation

HRID 2192771 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][C@@H:12]([C:14]([O:16][CH3:17])=[O:15])[CH2:11][C@@H:10](C(O)=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1(P([N:35]=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.C(N(CC)CC)C.C(O)C1C=CC=CC=1>C1(C)C=CC=CC=1>[NH2:35][C@@H:10]1[CH2:9][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:13][C@H:12]([C:14]([O:16][CH3:17])=[O:15])[CH2:11]1

Participants

6

Reactant 4

HCID 244Benzyl AlcoholHCID 8471Triethylamine2×HCID 199401P,P-Diphenylphosphinic azideHCID 11196951(3R,5S)-1-tert-butoxycarbonyl-5-methoxycarbonyl-piperidine-3-carboxylic acid

Product 1

HCID 53677987rel-1-(tert-butyl) 3-methyl (3R,5S)-5-aminopiperidine-1,3-dicarboxylate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

(3R*,5S*)-1-(tert-Butoxycarbonyl)-5-(methoxycarbonyl)piperidine-3-carboxylic acid (575 mg) was suspended in toluene (10 ml), diphenylphosphoryl azide (0.52 ml) and triethylamine (0.34 ml) were added and the mixture was stirred at 80° C. for 2 hr. The reaction mixture was cooled to room temperature, benzyl alcohol (0.52 ml) and triethylamine (0.34 ml) were added and the mixture was stirred at 80° C. for 2 hr. The reaction mixture was washed with water, 5% aqueous citric acid solution, saturated aqueous sodium hydrogen carbonate and saturated brine in this order, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography, and the fraction eluted with ethyl acetate-hexane (1:4) was concentrated under reduced pressure. The obtained residue was dissolved in methanol (5 ml), 10% palladium-carbon (50% containing water) (70 mg) was added, and the mixture was subjected to catalytic reduction at ambient temperature under a hydrogen atmosphere (1 atm) for 12 hr. The catalyst was filtered off, and the filtrate was concentrated under reduced pressure to give the object compound (370 mg) as an oil.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. stirringthe mixture was stirred at 80° C. for 2 hr
  3. washThe reaction mixture was washed with water, 5% aqueous citric acid solution, saturated aqueous sodium hydrogen carbonate and saturated brine in this order
  4. dry with materialdried over anhydrous sodium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography
  7. washthe fraction eluted with ethyl acetate-hexane (1:4)
  8. concentrationwas concentrated under reduced pressure
  9. dissolutionThe obtained residue was dissolved in methanol (5 ml)
  10. addition10% palladium-carbon (50% containing water) (70 mg) was added
  11. customwas subjected to catalytic reduction at ambient temperature under a hydrogen atmosphere
  12. customfor 12 hr
  13. filtrationThe catalyst was filtered off
  14. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-93732e23ea754c348923832309274fdd
Source dataset
uspto-grants-2012_12
Patent number
US08329691B2

Reaction notes

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