p-Toluenesulfonic acid → HCID 54491445, compound

HRID 651273Notes

Reaction equation

HRID 651273 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 3 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. 1H NMR (250 MHz, CDCl3): d: 7.35 (m, 5H), 4.5 (m, 1H), 3.8 (s, 3H), 3.4 (dd, 1H), 3.1 (m, 1H), 2.85 (m, 4H), 2.6 (m, 1H), 2.4 (m, 1H), 1.5 (s, 9H); MS (APCI): 362 (M+1).

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-0780be2de1d847c9997772d43a4f5e64
Source dataset
uspto-grants-2001_08
Patent number
US06278000B1

Reaction notes

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