HCID 19877037, compound → HCID 89815347, compound

HRID 1482960Notes

Reaction equation

HRID 1482960 reaction equation
[NH2:1][C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[C:4]([S:13][CH3:14])[CH:3]=1.[I:15]Cl.CC(O)=O>C(O)(=O)C.CCOC(C)=O>[NH2:1][C:2]1[C:12]([I:15])=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[C:4]([S:13][CH3:14])[CH:3]=1

Participants

5

Reactant 2

HCID 19877037HCID 19877037, compoundHCID 89814802HCID 89814802, compound

Product 1

HCID 89815347HCID 89815347, compoundYield 62.4%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a pre-heated 60° C. solution of ethyl 4-amino-2-(methylthio)benzoate (65 mmol) in acetic acid (150 mL) was added ICl/AcOH solution (1M, 72 mL, 72 mmol) dropwise during 40 min and the temperature was maintained at 60° C. for 3 h. After cooling to rt the reaction was diluted with EtOAc (500 mL) and washed with 5% sodium thiosulfate solution (3×100 mL) and brine (200 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by silica gel chromatography (0-20% EtOAc/Hexanes) to afford ethyl 4-amino-5-iodo-2-(methylthio)benzoate (13.67 g, 53% yield). For ethyl 4-amino-2-(methylthio)benzoate: LC-MS m/z 212 [M+H]+. For ethyl 4-amino-5-iodo-2-(methylthio)benzoate: LC-MS m/z 338 [M+H]+. 1H NMR (400 MHz, CDCl3): δ 8.29 (s, 1H), 6.47 (s, 1H), 4.49 (br s, 2H), 4.31 (q, J=7.2 Hz, 2H), 2.38 (s, 3H), 1.37 (t, J=7.2 Hz, 3H).

Workup

  1. temperatureAfter cooling to rt the reaction
  2. washwashed with 5% sodium thiosulfate solution (3×100 mL) and brine (200 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by silica gel chromatography (0-20% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-6123510905de47e68d8ddab0f0aa34f6
Source dataset
uspto-grants-2016_08
Patent number
US09416135B2

Reaction notes

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