Diiodomethane → 5-Iodo-4'-methyl-biphenyl-3-carboxylic acid (2-methoxy-1-methyl-ethyl)-amide

HRID 2266730Notes

Reaction equation

HRID 2266730 reaction equation
[CH3:1][O:2][CH2:3][CH:4]([NH:6][C:7]([C:9]1[CH:10]=[C:11]([C:16]2[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=2)[CH:12]=[C:13](N)[CH:14]=1)=[O:8])[CH3:5].N(OCCC(C)C)=O.[I:31]CI>>[CH3:1][O:2][CH2:3][CH:4]([NH:6][C:7]([C:9]1[CH:10]=[C:11]([C:16]2[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=2)[CH:12]=[C:13]([I:31])[CH:14]=1)=[O:8])[CH3:5]

Participants

4

Reactant 3

HCID 6346DiiodomethaneHCID 8053Isoamyl NitriteHCID 595997035-Amino-4'-methyl-biphenyl-3-carboxylic acid (2-methoxy-1-methyl-ethyl)-amide

Product 1

HCID 594325375-Iodo-4'-methyl-biphenyl-3-carboxylic acid (2-methoxy-1-methyl-ethyl)-amideYield 83.8%

Procedure

A mixture of 5-amino-4′-methyl-biphenyl-3-carboxylic acid (2-methoxy-1-methyl-ethyl)-amide (5.3 g, 17.8 mmol), iso-amyl nitrite (13.5 ml, 88.9 mmol) and diiodomethane (8 ml, 106.7 mmol) was stirred at room temperature for 1 hour. The mixture was then heated to 65° C. and kept for 8 hours, LC/MS indicated that reaction completed. The reaction mixture was cooled to room temperature and the separation of iodobenzene from excess diiodomethane was effected by addition of the reaction mixture at room temperature to a stirred solution of piperidin-CH3CN (V/V=90 ml/90 ml). A vigorous exothermic reaction ensued. The excess volatile reagents were removed by rotary evaporation at 80° C. The residue was diluted with ethyl acetate, washed with 10% hydrochloric acid, water and brine. The organic layer was separated and dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash column chromatography (ethyl acetate/hexanes=10:1) to yield 5-iodo-4′-methyl-biphenyl-3-carboxylic acid (2-methoxy-1-methyl-ethyl)-amide as a yellow solid (5.2 g, 83.8%). MS (M+H)=410.

Workup

  1. temperatureThe mixture was then heated to 65° C.
  2. waitkept for 8 hours
  3. customLC/MS indicated that reaction
  4. temperatureThe reaction mixture was cooled to room temperature
  5. customthe separation of iodobenzene from excess diiodomethane
  6. additionwas effected by addition of the reaction mixture at room temperature to a stirred solution of piperidin-CH3CN (V/V=90 ml/90 ml)
  7. customA vigorous exothermic reaction
  8. customThe excess volatile reagents were removed by rotary evaporation at 80° C
  9. additionThe residue was diluted with ethyl acetate
  10. washwashed with 10% hydrochloric acid, water and brine
  11. customThe organic layer was separated
  12. dry with materialdried over anhydrous Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. customThe residue was purified by flash column chromatography (ethyl acetate/hexanes=10:1)

Sources & evidence

ORD record
ord-04b2ebf3792548b486019a5d1ad286d7
Source dataset
uspto-grants-2010_12
Patent number
US07858654B2

Reaction notes

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