Benzyl Alcohol → 3-Benzyloxycarbonylamino-3-(1-methylallyl)piperidine-1-carboxylic acid tert-butyl ester

HRID 1912390Notes

Reaction equation

HRID 1912390 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C:10]([CH:17]([CH3:20])[CH:18]=[CH2:19])(C(O)=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([N:23]([CH2:26]C)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:35])C=CC=CC=1.[CH2:45]([OH:52])[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1>C1(C)C=CC=CC=1.CN(C)C1C=CN=CC=1.C(OCC)(=O)C.O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C:10]([NH:23][C:26]([O:52][CH2:45][C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)=[O:35])([CH:17]([CH3:20])[CH:18]=[CH2:19])[CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

9

Reactant 4

HCID 244Benzyl AlcoholHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 582932773-(1-Methylallyl)piperidine-1,3-dicarboxylic acid 1-tert-butyl ester

Product 1

HCID 582933873-Benzyloxycarbonylamino-3-(1-methylallyl)piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of an optically-active compound of 3-(1-methylallyl)piperidine-1,3-dicarboxylic acid 1-tert-butyl ester (1.02 g) and triethylamine (967 μl) in toluene (10 ml) heated to 90° C. was added dropwise diphenylphosphoryl azide (1.1 ml). The reaction mixture was stirred at the same temperature for 1 hour, and then thereto were added benzyl alcohol (718 μl) and 4-dimethylaminopyridine (127 mg). The mixture was stirred with refluxing overnight, then cooled to room temperature, and thereto were added water and ethyl acetate. The separated aqueous layer was extracted with ethyl acetate twice, and the combined organic layer was washed with water twice and saturated aqueous sodium chloride solution once, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent: chloroform/acetone=50/1). The resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=20/1 to 4/1) to give the titled compound (845 mg).

Workup

  1. stirringThe mixture was stirred
  2. temperaturewith refluxing overnight
  3. extractionThe separated aqueous layer was extracted with ethyl acetate twice
  4. washthe combined organic layer was washed with water twice
  5. dry with materialsaturated aqueous sodium chloride solution once, dried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified by silica gel column chromatography (eluent: chloroform/acetone=50/1)
  8. customThe resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=20/1 to 4/1)

Sources & evidence

ORD record
ord-b7940fd0801f43509a27b1082300dd37
Source dataset
uspto-grants-2013_12
Patent number
US08609647B2

Reaction notes

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