p-Toluenesulfonic acid → HCID 54491445, compound

HRID 381395Notes

Reaction equation

HRID 381395 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=[O:14])[CH:10]([CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].N1CCCC1.C1(C)C=CC(S(O)(=O)=O)=CC=1.Br[CH2:39][C:40]([O:42][CH3:43])=[O:41]>C1C=CC=CC=1.O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=[O:14])[C:10]([CH2:15][C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)([CH2:39][C:40]([O:42][CH3:43])=[O:41])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 31268PyrrolidineHCID 60984Methyl bromoacetateHCID 44607713tert-Butyl 3-benzyl-4-oxopiperidine-1-carboxylate

Product 1

HCID 54491445HCID 54491445, compound

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 962WaterSolvent

Procedure

A solution of the product from Step A of Example 21 above (1320 mg, 4.56 mmol), pyrrolidine (972 mg, 13 mmol) and p-toluenesulfonic acid (33 mg) in benzene (30 ml) was refluxed through 3A molecular sieves for about 17 h. The reaction mixture was cooled to room temperature and concentrated in vacuo. The residue was dissolved in benzene (10 ml) and cooled to about 0° C. Methyl bromoacetate (1530 mg, 10 mmol) was added dropwise. The reaction mixture was slowly allowed to warm to room temperature and then was heated under reflux for about 17 h at which point H2O (5 mL) was added. After refluxing for about another 2 h, the reaction mixture was cooled to room temperature and extracted with EtOAc (3×100 ml). The combined organic extracts were dried and concentrated in vacuo. The crude residue was chromatographed on SiO2-gel using 15% ethyl acetate/hexanes to give 280 mg of product.

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe residue was dissolved in benzene (10 ml)
  3. temperaturecooled to about 0° C
  4. temperatureto warm to room temperature
  5. temperaturewas heated
  6. additionwas added
  7. temperatureAfter refluxing for about another 2 h
  8. temperaturethe reaction mixture was cooled to room temperature
  9. extractionextracted with EtOAc (3×100 ml)
  10. customThe combined organic extracts were dried
  11. concentrationconcentrated in vacuo
  12. customThe crude residue was chromatographed on SiO2-gel

Sources & evidence

ORD record
ord-2be7f6838e6042fbb704e42cb44e63b2
Source dataset
uspto-grants-2001_10
Patent number
US06306875B1

Reaction notes

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