Diiodomethane → 5-Iodo-4'-methyl-biphenyl-3-carboxylic acid methyl ester

HRID 506610Notes

Reaction equation

HRID 506610 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([C:12]2[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][CH:13]=2)[CH:8]=[C:9](N)[CH:10]=1)=[O:4].N(OCCC(C)C)=O.[I:27]CI>N1CCCCC1.C(#N)C>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([C:12]2[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][CH:13]=2)[CH:8]=[C:9]([I:27])[CH:10]=1)=[O:4]

Participants

5

Reactant 3

HCID 6346DiiodomethaneHCID 8053Isoamyl NitriteHCID 57850917Methyl 5-amino-4'-methylbiphenyl-3-carboxylate

Product 1

HCID 578515885-Iodo-4'-methyl-biphenyl-3-carboxylic acid methyl esterYield 66%

Reagents, catalysts & solvents 1

HCID 20975722Piperidine acetonitrileSolvent

Procedure

A mixture of 5-amino-4′-methyl-biphenyl-3-carboxylic acid methyl ester (10.9 g, 45.2 mmol), iso-amyl nitrite (36.5 ml, 271.4 mmol) and diiodomethane (23 ml, 271.4 mmol) was stirred at room temperature for 1 hour. The mixture was then heated to 65° C. with stirring for 8 hours. The reaction mixture was cooled to room temperature and added to a stirred solution of piperidine/acetonitrile (180 mL, 1/1). A vigorous exothermic reaction ensued, after which volatiles were removed by rotary evaporation at 80° C. The residue was diluted with ethyl acetate, washed with 10% hydrochloric acid, water, brine, dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash column chromatography, eluting with hexanes, followed by hexanes/EtOAc=20:1, giving 5-iodo-4′-methyl-biphenyl-3-carboxylic acid methyl ester as white yellow solid (10.5 g, 66%). MS (M+H)=353.

Workup

  1. temperatureThe mixture was then heated to 65° C.
  2. stirringwith stirring for 8 hours
  3. temperatureThe reaction mixture was cooled to room temperature
  4. customA vigorous exothermic reaction
  5. customafter which volatiles were removed by rotary evaporation at 80° C
  6. additionThe residue was diluted with ethyl acetate
  7. washwashed with 10% hydrochloric acid, water, brine
  8. dry with materialdried over anhydrous Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by flash column chromatography
  12. washeluting with hexanes

Sources & evidence

ORD record
ord-6c829536c54e42adbe61da349c12ac58
Source dataset
uspto-grants-2010_08
Patent number
US07786110B2

Reaction notes

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