Allyl bromide → (RS)-alpha-Methyl-alpha-(2-propenyl)-3,5-bis(trifluoromethyl)benzeneacetic Acid

HRID 852677Notes

Reaction equation

HRID 852677 reaction equation
[CH2:1]([Li])[CH2:2][CH2:3]C.[CH3:6][CH:7]([C:11]1[CH:16]=[C:15]([C:17]([F:20])([F:19])[F:18])[CH:14]=[C:13]([C:21]([F:24])([F:23])[F:22])[CH:12]=1)[C:8]([OH:10])=[O:9].BrCC=C.S(=O)(O)[O-].[Na+]>O1CCCC1>[CH3:6][C:7]([CH2:3][CH:2]=[CH2:1])([C:11]1[CH:12]=[C:13]([C:21]([F:22])([F:23])[F:24])[CH:14]=[C:15]([C:17]([F:18])([F:19])[F:20])[CH:16]=1)[C:8]([OH:10])=[O:9]

Participants

6

Reactant 4

HCID 7841Allyl bromideHCID 115220582-(3,5-Bis(trifluoromethyl)phenyl)propanoic acidHCID 23665763Sodium BisulfiteHCID 178418339Butyllithium3×

Product 1

HCID 86594174(RS)-alpha-Methyl-alpha-(2-propenyl)-3,5-bis(trifluoromethyl)benzeneacetic AcidYield 49%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

n-Butyllithium (2.5M solution in hexanes, 61.0 mL, 153 mmol) was added slowly to a stirred, cooled (−78° C.) solution of (RS)-α-methyl-3,5-bis(trifluoromethyl)benzeneacetic acid (Description 7, 19.0 g, 66.4 mmol) in tetrahydrofuran (400 mL) and the mixture was stirred at −78° C. for 2 hours. Further n-butyllithium (2.5M solution in hexanes, 8.0 mL, 20 mmol) was added slowly and the mixture was stirred at −78° C. for 20 minutes. Further n-butyllithium (2.5M solution in hexanes, 8.0 mL, 20 mmol) was added slowly and the mixture was stirred at −78° C. for 20 minutes. 3-Bromo-1-propene (8.62 mL, 12.05 g, 100 mmol) was added slowly and the mixture was stirred at −78° C. for 30 minutes, then at room temperature for 1 hour. The mixture was poured into aqueous sodium bisulfite (10%, 500 mL) and extracted with ethyl acetate (2×500 mL). The combined organic fractions were washed with brine, dried (Na2SO4) and the solvent was evaporated under reduced pressure. The residue was triturated with hexane and the solid was collected and dried iii vacuo to give the title compound as a colourless solid (10.59 g, 49%). 1H NMR (400 MHz, CDCl3) δ 7.82 (2H, s), 7.81 (1H, s), 5.57 (1H, m), 5.13 (1H, s), 5.10 (1H, m), 2.86 (1H, m), 2.73 (1H, m), and 1.69 (3H, s).

Workup

  1. stirringthe mixture was stirred at −78° C. for 20 minutes
  2. stirringthe mixture was stirred at −78° C. for 20 minutes
  3. stirringthe mixture was stirred at −78° C. for 30 minutes
  4. waitat room temperature for 1 hour
  5. extractionextracted with ethyl acetate (2×500 mL)
  6. washThe combined organic fractions were washed with brine
  7. dry with materialdried (Na2SO4)
  8. customthe solvent was evaporated under reduced pressure
  9. customThe residue was triturated with hexane
  10. customthe solid was collected
  11. dry with materialdried iii vacuo

Sources & evidence

ORD record
ord-88f94f7a3c6a4529b6cdaea8578b7b61
Source dataset
uspto-grants-2007_08
Patent number
US07253205B2

Reaction notes

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