HCID 15548678, compound → HCID 15548679, compound

HRID 990774Notes

Reaction equation

HRID 990774 reaction equation
[CH2:1]([N:8]1[C:16]2([CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH:18]=[CH:17]2)[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]1=[O:29])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>C(Cl)(Cl)Cl.FC(F)(F)C(O)=O>[CH2:1]([N:8]1[C:16]2([CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:27])([CH3:26])[CH3:28])=[O:23])[CH2:18][CH2:17]2)[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]1=[O:29])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 1

HCID 15548678HCID 15548678, compound

Product 1

HCID 15548679HCID 15548679, compoundYield 19.9%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

To a solution of 2-benzyl-1′-tert-butoxycarbonyl-1′,6′-dihydrospiro[1H-isoindole-1,4′(5′H)-pyridine]-3(2H)-one (1.0 g) in chloroform (20 mL), trifluoroacetic acid (20 mL) was added and the mixture was stirred for 1 hour. The reaction mixture was concentrated. The residue was dissolved in methanol and hydrogenated with 4M hydrogen chloride/ethyl acetate in the presence of 20% palladium carbon at 1 atm of hydrogen for 14 hours. The catalyst was removed by filtration and the filtrate was concentrated. To the residue, aqueous 1N sodium hydroxide (5 mL), di-tert-butyl dicarbonate (655 mg) and dioxane (10 mL) were added and the mixture was stirred at room temperature for 4 hours. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was dried over anhydrous Na2SO4 and concentrated. The residue was purified by column chromatography on silica gel (hexane/ethyl acetate=4/1 to 1/2) to give the subject compound (200 mg).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionThe residue was dissolved in methanol and hydrogenated with 4M hydrogen chloride/ethyl acetate in the presence of 20% palladium carbon at 1 atm of hydrogen for 14 hours
  3. customThe catalyst was removed by filtration
  4. concentrationthe filtrate was concentrated
  5. additionTo the residue, aqueous 1N sodium hydroxide (5 mL), di-tert-butyl dicarbonate (655 mg) and dioxane (10 mL) were added
  6. stirringthe mixture was stirred at room temperature for 4 hours
  7. additionThe reaction mixture was poured into water
  8. extractionextracted with ethyl acetate
  9. dry with materialThe organic layer was dried over anhydrous Na2SO4
  10. concentrationconcentrated
  11. customThe residue was purified by column chromatography on silica gel (hexane/ethyl acetate=4/1 to 1/2)

Sources & evidence

ORD record
ord-255527719c7d42e1a46c06d84eed7649
Source dataset
uspto-grants-2002_10
Patent number
US06462053B1

Reaction notes

Loading…