Water → HCID 66666272, compound

HRID 1618026Notes

Reaction equation

HRID 1618026 reaction equation
C([O:3][C:4](=[O:24])[CH:5](C#N)[CH:6]([C:15]1[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][CH:16]=1)[C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][C:8]=1[F:14])C.O.OS(O)(=O)=O>C(O)(=O)C>[Br:21][C:18]1[CH:17]=[CH:16][C:15]([CH:6]([C:7]2[CH:12]=[CH:11][C:10]([F:13])=[CH:9][C:8]=2[F:14])[CH2:5][C:4]([OH:24])=[O:3])=[CH:20][CH:19]=1

Participants

5

Reactant 3

HCID 962WaterHCID 1118Sulfuric AcidHCID 666673303-(4-Bromo-phenyl)-2-cyano-3-(2,4-difluoro-phenyl)-propionic acid ethyl ester

Product 1

HCID 66666272HCID 66666272, compound

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 3-(4-bromo-phenyl)-2-cyano-3-(2,4-difluoro-phenyl)-propionic acid ethyl ester (2.4 g) in acetic acid (11 mL) was added water (6 mL) and concentrated H2SO4 (6.83 mL) at 0° C. The reaction mixture was heated to 120° C. overnight, then cooled and poured on ice and extracted with ethyl acetate (3×100 mL). The organic layers were washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The crude reaction product was purified by silica gel chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane/ethyl acetate (1:0 to 1:1) to provide the title compound as an off-white solid. MS (ESI−): m/z=339.0 ([M−H]−).

Workup

  1. temperaturecooled
  2. additionpoured on ice
  3. extractionextracted with ethyl acetate (3×100 mL)
  4. washThe organic layers were washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude reaction product
  9. customwas purified by silica gel chromatography
  10. washeluting with a gradient of n-heptane/ethyl acetate (1:0 to 1:1)

Sources & evidence

ORD record
ord-12a4be63e9ee47be8d160d0fe3ab9dd1
Source dataset
uspto-grants-2014_07
Patent number
US08765730B2

Reaction notes

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