Tetrahydrofuran → HCID 22618903, compound

HRID 842292Notes

Reaction equation

HRID 842292 reaction equation
Cl[C:2]([O:4][CH2:5]C)=[O:3].C(OC([C:12](CC)([CH2:16][CH2:17][CH2:18][CH2:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[CH:22][CH:21]=1)C(O)=O)=O)C.[N-:36]=[N+]=[N-].[Na+].[OH2:40].C1(C)C=CC(S(O)(=O)=O)=CC=1.[O:52]1[CH2:56][CH2:55]C[CH2:53]1>O.C1C=CC=CC=1.C(OCC)(=O)C.CO.C(N(CC)CC)C>[CH2:16]([C:17]([NH:36][C:2]([O:4][CH3:5])=[O:3])([CH2:18][CH2:19][C:20]1[CH:21]=[CH:22][C:23]([O:26][CH2:27][C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)=[CH:24][CH:25]=1)[C:53]([O:52][CH2:56][CH3:55])=[O:40])[CH3:12]

Participants

11

Reactant 5

HCID 8028TetrahydrofuranHCID 10928Ethyl chloroformateHCID 33557Sodium AzideHCID 521998p-Toluenesulfonic acid monohydrateHCID 22618906HCID 22618906, compound

Product 1

HCID 22618903HCID 22618903, compound

Reagents, catalysts & solvents 5

HCID 241BenzeneSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Triethylamine (45 ml) and ethyl chloroformate (21 ml) were added to a solution of 2-ethoxycarbonyl-2-ethyl-4-(2-(4-benzyloxyphenyl)ethyl)-butanoic acid (85 g) in tetrahydrofuran (430 ml) at 0° C. and the mixture was stirred at 0° C. for 35 minutes. A solution of sodium azide (14 g) in water (10 ml) was added thereto and the whole mixture was stirred at 0° for 3 hours. The reaction mixture was poured into ice-water and extracted with ethyl acetate. The ethyl acetate layer was washed with water and a saturated brine, dried over anhydrous sodium sulfate and the solvent was distilled away under reduced pressure to give a pale brown oily substance. The oily substance obtained was dissolved in benzene (300 ml) and the solution was refluxed under heating for 170 minutes. Methanol (50 ml) and p-toluenesulfonic acid monohydrate (catalytic amount) were added thereto and the mixture was further refluxed under heating for 10 minutes and allowed to stand at room temperature overnight. Ethyl acetate was added to the reaction mixture, and the mixture was washed with water and a saturated brine and dried over anhydrous sodium sulfate. The solvent was distilled away under reduced pressure and the residue obtained was purified by silica gel column chromatography (eluent; n-hexane:ethyl acetate=4:1) to give the subject compound (31 g).

Workup

  1. stirringthe whole mixture was stirred at 0° for 3 hours
  2. extractionextracted with ethyl acetate
  3. washThe ethyl acetate layer was washed with water
  4. dry with materiala saturated brine, dried over anhydrous sodium sulfate
  5. distillationthe solvent was distilled away under reduced pressure
  6. customto give a pale brown oily substance
  7. customThe oily substance obtained
  8. temperaturethe solution was refluxed
  9. temperatureunder heating for 170 minutes
  10. temperaturethe mixture was further refluxed
  11. temperatureunder heating for 10 minutes
  12. waitto stand at room temperature overnight
  13. washthe mixture was washed with water
  14. dry with materiala saturated brine and dried over anhydrous sodium sulfate
  15. distillationThe solvent was distilled away under reduced pressure
  16. customthe residue obtained
  17. customwas purified by silica gel column chromatography (eluent; n-hexane:ethyl acetate=4:1)

Sources & evidence

ORD record
ord-b11b6ec588a142528ed78cdca2a34fb4
Source dataset
uspto-grants-2002_04
Patent number
US06372800B1

Reaction notes

Loading…