tert-butyl 5,7-dichloro-2-(4-methoxybenzyl)-3-oxo-2',3'-dihydro-1'H-spiro[isoindoline-1,4'-pyridine]-1'-carboxylate → 5,7-dichloro-2',3'-dihydro-1'H-spiro[isoindoline-1,4'-pyridin]-3-one

HRID 390142Notes

Reaction equation

HRID 390142 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:20](=[C:21]([Cl:23])[CH:22]=1)[C:7]1([CH:12]=[CH:11][N:10](C(OC(C)(C)C)=O)[CH2:9][CH2:8]1)[N:6](CC1C=CC(OC)=CC=1)[C:5]2=[O:33]>C(O)(C(F)(F)F)=O.C(S(O)(=O)=O)(F)(F)F>[Cl:1][C:2]1[CH:3]=[C:4]2[C:20](=[C:21]([Cl:23])[CH:22]=1)[C:7]1([CH:8]=[CH:9][NH:10][CH2:11][CH2:12]1)[NH:6][C:5]2=[O:33]

Participants

4

Reactant 1

HCID 58295806tert-butyl 5,7-dichloro-2-(4-methoxybenzyl)-3-oxo-2',3'-dihydro-1'H-spiro[isoindoline-1,4'-pyridine]-1'-carboxylate

Product 1

HCID 582957155,7-dichloro-2',3'-dihydro-1'H-spiro[isoindoline-1,4'-pyridin]-3-oneYield 10.3%

Reagents, catalysts & solvents 2

HCID 6422Trifluoroacetic acidSolventHCID 62406Trifluoromethanesulfonic acidSolvent

Procedure

tert-Butyl 5,7-dichloro-2-(4-methoxybenzyl)-3-oxo-2′,3′-dihydro-1′H-spiro[isoindoline-1,4′-pyridine]-1′-carboxylate (3.5 g, 7.2 mmol) in TFA (36 mL) and CF3SO3H (4 mL) was heated to 60° C. for 5 h. The solvent was removed and satd aq NaHCO3 was added till pH=7. Then EtOAc was added, the organic layer was washed with brine, dried and concentrated to give the crude product. It was purified by preparative HPLC to give 5,7-dichloro-2′,3′-dihydro-1′H-spiro[isoindoline-1,4′-pyridin]-3-one (0.2 g, 10%). 1H NMR (CDCl3): 1.66 (m, 3H), 2.81 (m, 1H), 3.15 (m, 1H), 3.76 (m, 1H), 7.57 (m, 1H), 7.75 (m, 1H).

Workup

  1. customThe solvent was removed
  2. additionwas added till pH=7
  3. additionThen EtOAc was added
  4. washthe organic layer was washed with brine
  5. customdried
  6. concentrationconcentrated
  7. customto give the crude product
  8. customIt was purified by preparative HPLC

Sources & evidence

ORD record
ord-2d8cdb7f9f0245c591f8d006861d4bfe
Source dataset
uspto-grants-2013_02
Patent number
US08383629B2

Reaction notes

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