Trichloroacetyl chloride → HCID 10003659, compound

HRID 2082054Notes

Reaction equation

HRID 2082054 reaction equation
[Br-].[C:2]([CH:10]([N+:12]1[N:13]=[C:14]([CH2:32][CH2:33][CH2:34][CH3:35])[N:15]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[C:30]#[N:31])=[CH:20][CH:19]=2)[CH:16]=1)[CH3:11])(=O)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C([N:38](CC)CC)C.ClC(Cl)(Cl)C(Cl)=O>>[CH2:32]([C:14]1[N:15]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[C:30]#[N:31])=[CH:20][CH:19]=2)[C:16]2[N:12]([C:10]([CH3:11])=[C:2]([C:3]3[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=3)[N:38]=2)[N:13]=1)[CH2:33][CH2:34][CH3:35]

Participants

4

Reactant 3

HCID 6420Trichloroacetyl chlorideHCID 8471TriethylamineHCID 178441922HCID 178441922, compound

Product 1

HCID 10003659HCID 10003659, compoundYield 39%

Conditions

Temperature
80 °C

Procedure

A mixture of 303 mg (0.556 mmol) of 5-amino-1-(1-benzoylethyl-3-butyl-4-[(2'-cyanbiphenyl-4-yl)-methyl]-4H-1,2,4-triazolium bromide (from Step E) and 6 g of polyphosphoric acid was stirred at 80° C. under N2 for 5 hours. The cooled mixture was treated with an excess of ice. After the ice had melted, the water was decanted off, and the residue was partitioned between EtOAc and saturated aqueous NaHCO3. The organic phase was dried over Na2SO4, filtered, and concentrated in vacuo. The residual oil was dissolved in a minimum volume of CH2Cl2 and treated with 200 μl (145 mg, 1.43 mmol) of triethylamine. The resulting solution was cooled to 0° C. and stirred under N2 as 137 μl (223 mg, 1.23 mmol) of trichloroacetyl chloride was added. The solution was allowed to warm to room temperature. After 1 hour at room temperature, the solution was concentrated in vacuo. The residue was leached with 25 ml of ether. The filtered ether solution was washed with 25 ml of 0.2N HCl and then with 25 ml of 0.2N NaOH. The ethereal phase was dried (Na2SO4), filtered, and evaporated. Column chromatography of the residue on silica gel (elution with 99:1 and then 98:2 CH2Cl2 -MeOH) afforded 95.0 mg (39%) of the title compound as a brown solid of indefinite mp, suitable for use in the next step; homogeneous by TLC in 19:1 CH2Cl2 -MeOH.

Workup

  1. additionThe cooled mixture was treated with an excess of ice
  2. customthe water was decanted off
  3. customthe residue was partitioned between EtOAc and saturated aqueous NaHCO3
  4. dry with materialThe organic phase was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. dissolutionThe residual oil was dissolved in a minimum volume of CH2Cl2
  8. temperatureThe resulting solution was cooled to 0° C.
  9. additionwas added
  10. temperatureto warm to room temperature
  11. waitAfter 1 hour at room temperature
  12. concentrationthe solution was concentrated in vacuo
  13. washThe filtered ether solution was washed with 25 ml of 0.2N HCl
  14. dry with materialThe ethereal phase was dried (Na2SO4)
  15. filtrationfiltered
  16. customevaporated
  17. washColumn chromatography of the residue on silica gel (elution with 99:1

Sources & evidence

ORD record
ord-659bb39215d9409d82c8a6dba00474ce
Source dataset
uspto-grants-1993_02
Patent number
US05187179

Reaction notes

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