Triethylamine → 2-benzyl 5-methyl 6-amino-1,3-dihydro-2H-isoindole-2,5-dicarboxylate

HRID 604630Notes

Reaction equation

HRID 604630 reaction equation
[C:1]([O-:4])([O-])=[O:2].[K+].[K+].[CH3:7]CN(CC)CC.[NH2:14][C:15]1[CH:16]=[C:17]2[C:21](=[CH:22][C:23]=1I)[CH2:20][N:19]([C:25]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26])[CH2:18]2>CC#N.CO.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[NH2:14][C:15]1[CH:16]=[C:17]2[C:21]([CH2:20][N:19]([C:25]([O:27][CH2:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[O:26])[CH2:18]2)=[CH:22][C:23]=1[C:1]([O:4][CH3:7])=[O:2]

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 67057748benzyl 5-amino-6-iodo-1,3-dihydro-2H-isoindole-2-carboxylate

Product 1

HCID 670576842-benzyl 5-methyl 6-amino-1,3-dihydro-2H-isoindole-2,5-dicarboxylate

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 887MethanolSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

Palladium(II) acetate (46.1 mg, 0.0685 mmol), DPPF (38 mg, 0.0685 mmol), K2CO3 (284 mg, 2.06 mmol) and Et3N (95 uL, 0.685 mmol) were added to a solution of benzyl 5-amino-6-iodo-1,3-dihydro-2H-isoindole-2-carboxylate (270 mg, 0.685 mmol) in MeCN (5 mL) and MeOH (2.5 mL). The reaction mixture was purged with N2, the flask was capped and a CO balloon was attached to it. After bubbling CO gas into the solution through a needle attached to the balloon for 5 min, the mixture was heated under a CO balloon at 70° C. for 4 h. The mixture was diluted with EtOAc (50 mL), filtered through Celite, then washed with water (3×10 mL), brine (1×), dried (Na2SO4), filtered and the solvent was evaporated in vacuo. The residue was purified by flash chromatography on silica gel to provide 2-benzyl 5-methyl 6-amino-1,3-dihydro-2H-isoindole-2,5-dicarboxylate LCMS calc.=327.1; found=326.8 (M+H)+. 1H NMR (500 MHz, CDCl3): δ 7.80-7.75 (2 s, 1H); 7.45-7.35 (m, 5H); 6.61-6.55 (2 s, 1H); 5.79 (br s, 2H); 5.25 (s, 2H); 4.68 (t, J=13.5 Hz, 4H); 3.91-3.90 (2 s, 3H).

Workup

  1. customThe reaction mixture was purged with N2
  2. customthe flask was capped
  3. customAfter bubbling CO gas into the solution through a needle
  4. additionThe mixture was diluted with EtOAc (50 mL)
  5. filtrationfiltered through Celite
  6. washwashed with water (3×10 mL), brine (1×)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. customthe solvent was evaporated in vacuo
  10. customThe residue was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-b58eeda0384545a481e69e7fae49104a
Source dataset
uspto-grants-2011_03
Patent number
US07910592B2

Reaction notes

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