Benzyl Alcohol → benzyl {5-[2-(tetrahydro-2H-pyran-2-yloxy)ethyl]pyrazin-2-yl}carbamate

HRID 2192922Notes

Reaction equation

HRID 2192922 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][CH2:8][CH2:9][C:10]1[N:11]=[CH:12][C:13](C(O)=O)=[N:14][CH:15]=1.C([N:21]([CH2:24]C)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:33])C=CC=CC=1.[CH2:43]([OH:50])[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1>C1(C)C=CC=CC=1.O>[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][CH2:8][CH2:9][C:10]1[N:11]=[CH:12][C:13]([NH:21][C:24](=[O:33])[O:50][CH2:43][C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)=[N:14][CH:15]=1

Participants

7

Reactant 4

HCID 244Benzyl AlcoholHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 595710705-[2-(tetrahydro-2H-pyran-2-yloxy)ethyl]pyrazine-2-carboxylic acid

Product 1

HCID 59570908benzyl {5-[2-(tetrahydro-2H-pyran-2-yloxy)ethyl]pyrazin-2-yl}carbamate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

To a solution of 5-[2-(tetrahydro-2H-pyran-2-yloxy)ethyl]pyrazine-2-carboxylic acid (1.28 g) in toluene (20 mL) were added triethylamine (0.85 ml) and diphenylphosphoryl azide (1.3 mL) at room temperature, followed by stirring at room temperature for 15 minutes. The reaction solution was warmed to 90° C., followed by stirring for 30 minutes. To the reaction solution was added benzyl alcohol (1.05 mL), followed by reflux for 3 hours. After leaving it to be cooled to room temperature, water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was sequentially washed with saturated aqueous sodium bicarbonate and saturated brine, and dried over anhydrous magnesium sulfate. After filtration and concentration, the obtained crude product was purified by silica gel column chromatography (hexane:ethyl acetate=5:1-2:1). The obtained solid was collected by filtration while washing with a solvent (hexane:diisopropyl ether=5:1), to obtain benzyl {5-[2-(tetrahydro-2H-pyran-2-yloxy)ethyl]pyrazin-2-yl}carbamate (461 mg) as a white solid.

Workup

  1. temperatureThe reaction solution was warmed to 90° C.
  2. stirringby stirring for 30 minutes
  3. temperatureby reflux for 3 hours
  4. customAfter leaving it
  5. temperatureto be cooled to room temperature
  6. extractionfollowed by extraction with ethyl acetate
  7. washThe organic layer was sequentially washed with saturated aqueous sodium bicarbonate and saturated brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationAfter filtration and concentration
  10. customthe obtained crude product
  11. customwas purified by silica gel column chromatography (hexane:ethyl acetate=5:1-2:1)
  12. filtrationThe obtained solid was collected by filtration
  13. washwhile washing with a solvent (hexane:diisopropyl ether=5:1)

Sources & evidence

ORD record
ord-6c5af4e955ed4fc6800d35faa748135b
Source dataset
uspto-grants-2012_12
Patent number
US08329707B2

Reaction notes

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