Benzyl Alcohol → Methyl 5-(benzyloxycarbonylamino)bicyclo[3.2.1]octane-1-carboxylate

HRID 1408860Notes

Reaction equation

HRID 1408860 reaction equation
[CH3:1][O:2][C:3]([C:5]12[CH2:13][C:9](C(O)=O)([CH2:10][CH2:11][CH2:12]1)[CH2:8][CH2:7]C2)=[O:4].C1C=CC(OP([O:29][C:30]2C=CC=CC=2)(N=[N+]=[N-])=O)=CC=1.C([N:38](CC)CC)C.[CH2:43]([OH:50])[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1>C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH2:43]([O:50][C:30]([NH:38][C:9]12[CH2:13][C:5]([C:3]([O:2][CH3:1])=[O:4])([CH2:7][CH2:8]1)[CH2:12][CH2:11][CH2:10]2)=[O:29])[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1

Participants

7

Reactant 4

HCID 244Benzyl AlcoholHCID 8471TriethylamineHCID 123414Diphenylphosphoryl azideHCID 7272255-(Methoxycarbonyl)bicyclo[3.3.1]nonane-1-carboxylic acid

Product 1

HCID 68048076Methyl 5-(benzyloxycarbonylamino)bicyclo[3.2.1]octane-1-carboxylateYield 127.6%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 5-(methoxycarbonyl)bicyclo[3.3.1]nonane-1-carboxylic acid (5.23 g, 24.7 mmol), diphenylphosphonic azide (8.0 mL, 36.9 mmol) and triethylamine (1.0 mL, 136 mmol) in toluene (150 mL) was stirred at room temperature for one hour, and then refluxed for three hours. Benzyl alcohol (4.0 mL, 38.7 mmol) was added, and the mixture was continued to reflux overnight. After cooled to room temperature, the reaction mixture was diluted with ethyl acetate (100 mL), washed with Sat. NaHCO3 and brine, dried over sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate: 20/1) to afford 10 g of methyl 5-(benzyloxycarbonylamino)bicyclo-[3.2.1]octane-1-carboxylate (containing BnOH) as a brown oil. ESI-MS m/z: 318 (M+H)+. It was used in the next step without purification.

Workup

  1. temperaturerefluxed for three hours
  2. temperatureto reflux overnight
  3. temperatureAfter cooled to room temperature
  4. washwashed with Sat. NaHCO3 and brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate: 20/1)

Sources & evidence

ORD record
ord-5572d9239b634be4bca78594d7f2b189
Source dataset
uspto-grants-2014_12
Patent number
US08921370B2

Reaction notes

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