Iodine chloride → benzyl 5-amino-6-iodo-1,3-dihydro-2H-isoindole-2-carboxylate

HRID 604629Notes

Reaction equation

HRID 604629 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH2:7][N:6]([C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12])[CH2:5]2.C([O-])(O)=O.[Na+].[I:26]Cl>C(Cl)Cl.CO>[NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[I:26])[CH2:7][N:6]([C:11]([O:13][CH2:14][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)=[O:12])[CH2:5]2

Participants

6

Reactant 3

HCID 24640Iodine chlorideHCID 516892Sodium BicarbonateHCID 67057746Benzyl 5-aminoisoindoline-2-carboxylate

Product 1

HCID 67057748benzyl 5-amino-6-iodo-1,3-dihydro-2H-isoindole-2-carboxylate

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of benzyl 5-amino-1,3-dihydro-2H-isoindole-2-carboxylate (560 mg, 2.09 mmol) in a mixture of CH2Cl2 (10 mL) and MeOH (2.5 mL), was added NaHCO3 (263 mg, 3.13 mmol) followed by 1M ICl in CH2Cl2 (2.1 mL, 2.1 mmol). The mixture was stirred for 30 min and then quenched with sat. aq. NaHSO3. The resulting mixture was extracted with EtOAc (3×). The combined organic layers were washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica gel to provide benzyl 5-amino-6-iodo-1,3-dihydro-2H-isoindole-2-carboxylate. LCMS calc.=395.0; found=394.7 (M+H)+. 1H NMR (500 MHz, CDCl3): δ 7.58-7.51 (2 s, 1H); 7.45-7.35 (m, 5H); 6.70-6.64 (2 s, 1H); 5.24 (s, 2H); 4.67 (s, 2H); 4.65 (s, 2H); 4.15 (br, s, 2H).

Workup

  1. customquenched with sat. aq. NaHSO3
  2. extractionThe resulting mixture was extracted with EtOAc (3×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-cb5404586f224167821a966ffcdaf379
Source dataset
uspto-grants-2011_03
Patent number
US07910592B2

Reaction notes

Loading…