Butyl bromide → HCID 66619669, compound

HRID 415606Notes

Reaction equation

HRID 415606 reaction equation
[NH2:1][C:2]([C:4]1[C:5]([F:18])=[C:6]([CH:14]=[CH:15][C:16]=1[F:17])[O:7][CH2:8][CH:9]=[CH:10][C:11]([OH:13])=[O:12])=[O:3].C([O-])([O-])=O.[K+].[K+].[CH2:25](Br)[CH2:26][CH2:27][CH3:28]>CN(C=O)C.O>[NH2:1][C:2]([C:4]1[C:5]([F:18])=[C:6]([CH:14]=[CH:15][C:16]=1[F:17])[O:7][CH2:8][CH:9]=[CH:10][C:11]([O:13][CH2:25][CH2:26][CH2:27][CH3:28])=[O:12])=[O:3]

Participants

6

Reactant 3

HCID 8002Butyl bromideHCID 11430Potassium CarbonateHCID 66619734HCID 66619734, compound

Product 1

HCID 66619669HCID 66619669, compoundYield 57%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

4-[3-(Aminocarbonyl)-2,4-difluorophenoxy]-2-butenoic acid, mixture of isomeres (3:2) E:Z, (526 mg, 2 mmol, 1 equiv.) was dissolved in dry DMF (5 ml). K2CO3 (850 mg, 6 mmol, 3 equiv.) and n-butylbromide (0.23 ml, 2.1 mmol, 1.05 equiv.) were added and the reaction mixture was heated for 70 h at 50° C. and for 1.5 h at r.t. After cooling at r.t., the mixture was diluted with H2O (50 ml) and extracted with EtOAc (3×40 ml). The combined organic extracts were washed with H2O (6×30 ml), dried (MgSO4) and evaporated to dryness under reduced pressure. The oily residue was purified by column chromatography on silica, eluted with CH2Cl2 and MeOH/CH2Cl2 (1%), to give 364 mg, 57% yield, mp<40° C. HPLC-MS (method 1): m/z 314 [M+H]+, Rt=3.88 min. By 1H-NMR analysis it was determined to be a mixture of isomeres in a ratio (5:7) E:Z. When the same reaction was performed on the acid (3:40) E:Z mixture of isomeres, the product obtained was determined to be a mixture of isomeres in a ratio (1:4) E:Z.

Workup

  1. temperatureAfter cooling at r.t.
  2. extractionextracted with EtOAc (3×40 ml)
  3. washThe combined organic extracts were washed with H2O (6×30 ml)
  4. dry with materialdried (MgSO4)
  5. customevaporated to dryness under reduced pressure
  6. customThe oily residue was purified by column chromatography on silica
  7. washeluted with CH2Cl2 and MeOH/CH2Cl2 (1%)
  8. customto give 364 mg, 57% yield, mp<40° C
  9. additiona mixture of isomeres in a ratio (5:7) E
  10. customWhen the same reaction
  11. additionZ mixture of isomeres
  12. customthe product obtained
  13. additiona mixture of isomeres in a ratio (1:4) E

Sources & evidence

ORD record
ord-612d45ce3b0f48049d773c507cdbb6a6
Source dataset
uspto-grants-2012_01
Patent number
US08088791B2

Reaction notes

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