Benzyl Alcohol → 1-tert-butyl 3-methyl(3R,5S)-5-{[(benzyloxy)carbonyl]amino}piperidine-1,3-dicarboxylate

HRID 2192792Notes

Reaction equation

HRID 2192792 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=[N+]=[N-])(C2C=CC=CC=2)=[O:28])C=CC=CC=1.C([N:40]([CH2:43]C)CC)C.[CH2:45]([OH:52])[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1>C1(C)C=CC=CC=1>[CH2:45]([O:52][C:43]([NH:40][C@@H:10]1[CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:13][C@H:12]([C:14]([O:16][CH3:17])=[O:15])[CH2:11]1)=[O:28])[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=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 541184661-tert-butyl 3-methyl(3R,5S)-5-{[(benzyloxy)carbonyl]amino}piperidine-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, and the residue was dissolved in ethyl acetate, washed with water, 0.5 M hydrochloric acid, saturated aqueous sodium hydrogen carbonate 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 the fraction eluted with ethyl acetate-hexane (1:3-3:1) was concentrated under reduced pressure to give the object compound (2.78 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. washwashed with water, 0.5 M hydrochloric acid, saturated aqueous sodium hydrogen carbonate and saturated brine in this order
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customThe solvent was evaporated under reduced pressure
  8. washthe fraction eluted with ethyl acetate-hexane (1:3-3:1)
  9. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-6f6cb09f936f43d8bb7651d372b61155
Source dataset
uspto-grants-2012_12
Patent number
US08329691B2

Reaction notes

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