Acetic Acid → HCID 117701582, compound

HRID 1507429Notes

Reaction equation

HRID 1507429 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([CH3:36])=[C:11](C2(C([O-])=O)CN(C(OCC3C=CC=CC=3)=O)C2)[C:12]([C:15](=[O:18])[CH2:16][CH3:17])=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[C:39]([OH:42])(=O)[CH3:40].Cl.[CH3:44][N:45]([CH3:48])[CH:46]=[O:47]>CO>[CH2:1]([O:8][C:9]1[C:10]([CH3:36])=[C:11]2[C:12]([C:15](=[O:18])[C:16]([CH3:17])=[C:1]([CH:2]3[CH2:48][N:45]([C:46]([O:42][CH2:39][C:40]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)=[O:47])[CH2:44]3)[O:8]2)=[CH:13][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 131734371HCID 131734371, compound

Product 1

HCID 117701582HCID 117701582, compoundYield 11%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 1-benzyl 3-[3-(benzyloxy)-2-methyl-6-propanoylphenyl]azetidine-1,3-dicarboxylate (2.77 g, 5.68 mmol) obtained in Example 1-1 in dimethylformamide (16 mL), 60% sodium hydride (568 mg, 14.2 mmol) was added in small portions under cooling with ice, and then the mixture was brought back to room temperature and stirred for 1 hour. The reaction solution was cooled with ice. Then, acetic acid (1.30 mL, 22.7 mmol) was added dropwise thereto, subsequently methanol (40 mL) and concentrated hydrochloric acid (4 mL) were added thereto, and the mixture was heated with stirring at a bath temperature of 75° C. for 3 hours. The reaction solution was allowed to cool, and then methanol in the mixture was distilled off under reduced pressure. Water was added to the obtained residue, followed by extraction with ethyl acetate. The organic layer was washed with water and then dried over magnesium sulfate. The desiccant was filtered off, and then the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=80/20→50/50) to obtain 295 mg of the title compound (yield: 11%).

Workup

  1. temperatureunder cooling with ice
  2. customwas brought back to room temperature
  3. temperatureThe reaction solution was cooled with ice
  4. temperaturethe mixture was heated
  5. stirringwith stirring at a bath temperature of 75° C. for 3 hours
  6. temperatureto cool
  7. distillationmethanol in the mixture was distilled off under reduced pressure
  8. additionWater was added to the obtained residue
  9. extractionfollowed by extraction with ethyl acetate
  10. washThe organic layer was washed with water
  11. dry with materialdried over magnesium sulfate
  12. filtrationThe desiccant was filtered off
  13. concentrationthe filtrate was concentrated under reduced pressure
  14. customThe obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=80/20→50/50)

Sources & evidence

ORD record
ord-2473447931e741de8bd74fb35418dc78
Source dataset
uspto-grants-2015_12
Patent number
US09221811B2

Reaction notes

Loading…