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

HRID 1259885Notes

Reaction equation

HRID 1259885 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, the residue was dissolved in ethyl acetate, 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 to give the object product (2.79 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, 0.5M 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

Sources & evidence

ORD record
ord-5cddf5136e264bb4bb95798c9b3ee598
Source dataset
uspto-grants-2013_06
Patent number
US08466282B2

Reaction notes

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