4-Iodoaniline → HCID 67486301, compound

HRID 1755184Notes

Reaction equation

HRID 1755184 reaction equation
[CH3:1][O:2][C:3](=[O:22])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH:11]([C:19]([OH:21])=O)[C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:6][CH:5]=1.C(Cl)(=O)C(Cl)=O.[I:29][C:30]1[CH:36]=[CH:35][C:33]([NH2:34])=[CH:32][CH:31]=1>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:22])[C:4]1[CH:5]=[CH:6][C:7]([CH2:10][CH:11]([C:12]2[CH:13]=[CH:14][C:15]([OH:18])=[CH:16][CH:17]=2)[C:19](=[O:21])[NH:34][C:33]2[CH:35]=[CH:36][C:30]([I:29])=[CH:31][CH:32]=2)=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 108934-IodoanilineHCID 65578Oxalyl chlorideHCID 67486387HCID 67486387, compound

Product 1

HCID 67486301HCID 67486301, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred suspension of 4-[2-carboxy-2-(4-hydroxy-phenyl)-ethyl]-benzoic acid methyl ester (Step C, 1.5 g, 5.0 mmol) in anhydrous CH2Cl2 (10 mL), was added oxalylchloride (1.57 g, 12.5 mmol) at rt, the reaction mixture was stirred for 14 h. The reaction mixture was concentrated under reduced pressure and azeotroped with CH2Cl2 (2×10 mL) dried under vacuum for 3 h, The crude acid chloride (1.8 g, 5.66 mmol) was treated with 4-iodoaniline (1.48 g, 6.79 mmol) and N,N-diispropylethylamine (3.0 mL, 16.9 mmol) in CH2Cl2 at 0° C. The reaction mixture was stirred for 14 h at rt and the reaction mixture was concentrated under reduced pressure. The mixture was extracted with ethyl acetate (100 mL) and the organic layer was washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The residue was treated with CH2Cl2 to get solid compound, which was filtered and washed with CH2Cl2 to give 4-[2-(4-hydroxy-phenyl)-2-(4-iodo-phenyl-carbamoyl)-ethyl]-benzoic acid methyl ester as a yellowish solid (1.6 g, 64%): 1H NMR (300 MHz, DMSO-d6): δ 10.05 (s, 1H, NH), 9.28 (s, 1H, OH), 7.81 (d, J=8.1 Hz, 2H), 7.53 (d, J=8.7 Hz, 2H), 7.31 (t, J=8.4 Hz, 4H), 7.18 (d, J=8.4 Hz, 2H), 6.65 (d, J=8.4 Hz, 2H), 3.85 (t, J=6.9 Hz, 1H), 3.77 (s, 3H), 3.40-3.36 (m, 1H), 2.95 (dd, J=6.0, 12.9 Hz, 1H); TLC conditions: Uniplate silica gel, 250 microns; mobile phase=ethyl acetate/hexanes (1:2); Rf=0.5.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customazeotroped with CH2Cl2 (2×10 mL)
  3. customdried under vacuum for 3 h
  4. stirringThe reaction mixture was stirred for 14 h at rt
  5. concentrationthe reaction mixture was concentrated under reduced pressure
  6. extractionThe mixture was extracted with ethyl acetate (100 mL)
  7. washthe organic layer was washed with brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated under reduced pressure
  10. additionThe residue was treated with CH2Cl2
  11. customto get solid compound, which
  12. filtrationwas filtered
  13. washwashed with CH2Cl2

Sources & evidence

ORD record
ord-cd2bb8b7a4884df5aa3e542dd849910d
Source dataset
uspto-grants-2015_10
Patent number
US09169201B2

Reaction notes

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