Triphenyl Phosphate → 4-cyano-3-(2'-cyano-biphenyl-4-yl)-1-methyl-5-trifluoromethyl-1H-pyrrole-2-carboxylic acid ethyl ester

HRID 1865114

Reaction equation

HRID 1865114 reaction equation
[C:1]([C:3]1[C:4]([C:18]2[CH:23]=[CH:22][C:21](OS(C(F)(F)F)(=O)=O)=[CH:20][CH:19]=2)=[C:5]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[N:6]([CH3:12])[C:7]=1[C:8]([F:11])([F:10])[F:9])#[N:2].[C:32]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1B(O)O)#[N:33].C1(OP(OC2C=CC=CC=2)(OC2C=CC=CC=2)=O)C=CC=CC=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[CH2:16]([O:15][C:13]([C:5]1[N:6]([CH3:12])[C:7]([C:8]([F:9])([F:10])[F:11])=[C:3]([C:1]#[N:2])[C:4]=1[C:18]1[CH:23]=[CH:22][C:21]([C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=2[C:32]#[N:33])=[CH:20][CH:19]=1)=[O:14])[CH3:17]

Participants

7

Reactant 4

HCID 8289Triphenyl PhosphateHCID 62657Potassium Phosphate, TribasicHCID 27346102-Cyanophenylboronic acidHCID 86611446Ethyl 4-cyano-1-methyl-5-(trifluoromethyl)-3-{4-[(trifluoromethyl)sulfonyloxy]phenyl}pyrrole-2-carboxylate

Product 1

HCID 690203034-cyano-3-(2'-cyano-biphenyl-4-yl)-1-methyl-5-trifluoromethyl-1H-pyrrole-2-carboxylic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Procedure

Prepare the title compound in a manner analogous to the procedure described in Scheme IIIa. For example, place ethyl 4-cyano-1-methyl-5-(trifluoromethyl)-3-{4-[(trifluoromethyl)sulfonyloxy]phenyl}pyrrole-2-carboxylate (11.0 mmol, prepared in example E-277), 2-cyano-phenyl boronic acid (1.5 mmol), palladium (II) acetate (0.12 mmol), triphenylphosphate (0.24 mmol), and tribasic potassium phosphate (3.6 mmol) in a round bottom flask and add dioxane. Heat reaction to reflux for 18 hours, remove the heat and wash with water while extracting with ethyl acetate. Dry organics with sodium sulfate, filter, and concentrate in vacuo. Purify the residue via radial chromatography eluting with methylene chloride, ethyl acetate and hexane to provide the title compound.

Workup

  1. temperatureHeat
  2. customreaction
  3. temperatureto reflux for 18 hours
  4. customremove the
  5. temperatureheat
  6. washwash with water
  7. extractionwhile extracting with ethyl acetate
  8. filtrationDry organics with sodium sulfate, filter
  9. concentrationconcentrate in vacuo
  10. customPurify the residue via radial chromatography
  11. washeluting with methylene chloride, ethyl acetate and hexane

Sources & evidence

ORD record
ord-ffa9f4a52e6b4dd1b4dda9fa526e2679
Source dataset
uspto-grants-2009_12
Patent number
US07625932B2

Linked notes

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