(1S)-1-(3-Ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethylamine → (S)-4-amino-2-[1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-5-methoxy-isoindole-1,3-dione

HRID 532117Notes

Reaction equation

HRID 532117 reaction equation
[NH2:1][C:2]1[C:12]([O:13][CH3:14])=[CH:11][CH:10]=[C:4]2[C:5]([O:7][C:8](=[O:9])[C:3]=12)=[O:6].[CH2:15]([O:17][C:18]1[CH:19]=[C:20]([C@H:26]([NH2:32])[CH2:27][S:28]([CH3:31])(=[O:30])=[O:29])[CH:21]=[CH:22][C:23]=1[O:24][CH3:25])[CH3:16]>C(O)(=O)C>[NH2:1][C:2]1[C:12]([O:13][CH3:14])=[CH:11][CH:10]=[C:4]2[C:5]([O:7][C:8](=[O:9])[C:3]=12)=[O:6].[NH2:1][C:2]1[C:12]([O:13][CH3:14])=[CH:11][CH:10]=[C:4]2[C:3]=1[C:8](=[O:9])[N:32]([C@@H:26]([C:20]1[CH:21]=[CH:22][C:23]([O:24][CH3:25])=[C:18]([O:17][CH2:15][CH3:16])[CH:19]=1)[CH2:27][S:28]([CH3:31])(=[O:30])=[O:29])[C:5]2=[O:7]

Participants

5

Reactant 2

HCID 11282264(1S)-1-(3-Ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethylamineHCID 866677923-Amino-4-methoxy-phthalic anhydride

Product 2

HCID 68088801(S)-4-amino-2-[1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-5-methoxy-isoindole-1,3-dioneHCID 866677923-Amino-4-methoxy-phthalic anhydride

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

3-Amino-4-methoxy-phthalic anhydride is prepared according to a procedure based on Rudolf Grewe (Berichte der Deutschen Chemischen Gesellschaft [Abteilung] B: Abhandlungen (1938), 71B 907-11). A stirred mixture of 3-amino-4-methoxy-phthalic anhydride (1 mmol) and (S)-1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethylamine (1 mmol) in acetic acid is heated to reflux overnight. The solvent is removed in vacuo. The residue is extracted with water and ethyl acetate. The organic layer is dried over MgSO4. The solvent is removed in vacuo to give the crude (S)-4-amino-2-[1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-5-methoxy-isoindole-1,3-dione. The product is purified by column chromatography or recrystallization. To a stirred solution of (S)-4-amino-2-[1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-5-methoxy-isoindole-1,3-dione (0.5 mmol) in anhydrous CH2Cl2, is added iodotrimethylsilane (3 mmol). The mixture is stirred at room temperature for 24 hours. The reaction mixture is diluted with brine and is extracted with CH2Cl2. The solvent is removed in vacuo to afford crude (S)-4-amino-2-[1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-5-hydroxy-isoindole-1,3-dione. The product is purified by column chromatography or recrystallization.

Workup

  1. temperatureis heated
  2. temperatureto reflux overnight
  3. customThe solvent is removed in vacuo
  4. extractionThe residue is extracted with water and ethyl acetate
  5. dry with materialThe organic layer is dried over MgSO4
  6. customThe solvent is removed in vacuo

Sources & evidence

ORD record
ord-902eca985ef941909bacec65b0aca425
Source dataset
uspto-grants-2014_10
Patent number
US08853175B2

Reaction notes

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