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

HRID 1509380Notes

Reaction equation

HRID 1509380 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 11358159rel-1-(1,1-Dimethylethyl) 3-methyl (3R,5S)-1,3,5-piperidinetricarboxylate

Product 1

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

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

(3S,5R)-1-(tert-Butoxycarbonyl)-5-(methoxycarbonyl)piperidine-3-carboxylic acid (2.83 g) was suspended in toluene (36 ml), diphenylphosphoryl azide (2.60 ml) and triethylamine (1.70 ml) were added, and the mixture was stirred at 100° C. for 1 hr. The reaction mixture was cooled to room temperature, benzyl alcohol (1.53 ml) and triethylamine (7.00 ml) were added and the mixture was stirred at 80° C. for 3 hr. The reaction mixture was concentrated, the residue was dissolved in ethyl acetate, and the solution was washed with water, 0.5M hydrochloric acid, and saturated brine in this order, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography, and a fraction eluted with ethyl acetate-hexane (1:3-3:1) was concentrated under reduced pressure. The obtained residue was dissolved in methanol (60 ml), 10% palladium carbon (50% in water) (150 mg) was added and the mixture was stirred under a hydrogen pressurization (5 atom) at ambient temperature for 5 hr. The catalyst was filtered off, and the filtrate was concentrated under reduced pressure to give the object product (1.83 g) as an oil.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. stirringthe mixture was stirred at 80° C. for 3 hr
  3. concentrationThe reaction mixture was concentrated
  4. dissolutionthe residue was dissolved in ethyl acetate
  5. washthe solution was washed with water, 0.5M hydrochloric acid, and saturated brine in this order
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customThe solvent was evaporated under reduced pressure
  8. washa fraction eluted with ethyl acetate-hexane (1:3-3:1)
  9. concentrationwas concentrated under reduced pressure
  10. dissolutionThe obtained residue was dissolved in methanol (60 ml)
  11. addition10% palladium carbon (50% in water) (150 mg) was added
  12. stirringthe mixture was stirred under a hydrogen pressurization (5 atom) at ambient temperature for 5 hr
  13. filtrationThe catalyst was filtered off
  14. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-cd9c5f28dd074157a7ad49150dc951b9
Source dataset
uspto-grants-2015_12
Patent number
US09221836B2

Reaction notes

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