1-Bromo-4-ethylbenzene → Ethyl 2-(4-ethylphenyl)-4,4,4-trifluoro-3-methylbutanoate

HRID 1475637Notes

Reaction equation

HRID 1475637 reaction equation
[F:1][C:2]([F:12])([F:11])[CH:3]([CH3:10])[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].C[Si](C)(C)[N-][Si](C)(C)C.[Li+].Br[C:24]1[CH:29]=[CH:28][C:27]([CH2:30][CH3:31])=[CH:26][CH:25]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[CH2:30]([C:27]1[CH:28]=[CH:29][C:24]([CH:4]([CH:3]([CH3:10])[C:2]([F:11])([F:12])[F:1])[C:5]([O:7][CH2:8][CH3:9])=[O:6])=[CH:25][CH:26]=1)[CH3:31]

Participants

7

Reactant 4

HCID 153131-Bromo-4-ethylbenzeneHCID 228896Ethyl 3-methyl-4,4,4-trifluorobutanoateHCID 2733832Lithium HexamethyldisilazideHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenyl

Product 1

HCID 67959523Ethyl 2-(4-ethylphenyl)-4,4,4-trifluoro-3-methylbutanoate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent3×

Procedure

Under argon, a solution of 1.29 g (7.02 mmol) of (+/−)-ethyl 4,4,4-trifluoro-3-methylbutanoate in 2 ml of abs. toluene was added dropwise to 8.1 ml of a 1 M solution, cooled to −10° C., of lithium hexamethyldisilazide in toluene (8.1 mmol). After 10 min at −10° C., a mixture of 1.0 g (5.4 mmol) of 1-bromo-4-ethylbenzene, 36.4 mg (0.16 mmol) of palladium(II) acetate and 134 mg (0.34 mmol) of 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl in 5 ml of abs. toluene was added to this reaction mixture. After the addition had ended, the mixture was warmed to RT and then stirred first at RT for 1 h and then at 80° C. for a further 3 h. After cooling to RT, the precipitated salts were filtered off with suction, the residue was washed with toluene and the combined filtrates were concentrated under reduced pressure. This gave 1.26 g of crude product (80.9% of theory) which was reacted as such.

Workup

  1. additionAfter the addition
  2. waitat 80° C. for a further 3 h
  3. temperatureAfter cooling to RT
  4. filtrationthe precipitated salts were filtered off with suction
  5. washthe residue was washed with toluene
  6. concentrationthe combined filtrates were concentrated under reduced pressure
  7. customThis gave 1.26 g of crude product (80.9% of theory) which was reacted as such

Sources & evidence

ORD record
ord-6eb6afa9c98144c4b413f1ba47550770
Source dataset
uspto-grants-2015_04
Patent number
US09018258B2

Reaction notes

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