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

HRID 217342Notes

Reaction equation

HRID 217342 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.CC#N>[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. and kept at this temperature for 8 hours. The reaction mixture to room temperature and then added to a stirred solution of piperidine/CH3CN (V:V=90 ml:90 ml). A vigorous exothermic reaction ensued. The excess volatile reagents were removed by rotary evaporation. 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 n-hexane, followed by n-hexane/ethyl acetate (20:1), giving 5-Iodo-4′-methyl-biphenyl-3-carboxylic acid methyl ester as white yellow solid (10.5 g, 66%).

Workup

  1. temperatureThe mixture was then heated to 65° C.
  2. waitkept at this temperature for 8 hours
  3. customA vigorous exothermic reaction
  4. customThe excess volatile reagents were removed by rotary evaporation
  5. additionThe residue was diluted with ethyl acetate
  6. washwashed with 10% hydrochloric acid, water, brine
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by flash column chromatography
  11. washeluting with n-hexane

Sources & evidence

ORD record
ord-2ba2a7a7e115431e8a07fc5a25cfe8fd
Source dataset
uspto-grants-2012_06
Patent number
US08193368B2

Reaction notes

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