1-Bromo-4-fluorobenzene → HCID 68170292, compound

HRID 1475636Notes

Reaction equation

HRID 1475636 reaction equation
[CH:1]1([CH2:6][C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:5][CH2:4][CH2:3][CH2:2]1.C[Si](C)(C)[N-][Si](C)(C)C.[Li+].Br[C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=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>[CH:1]1([CH:6]([C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=2)[C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 99931-Bromo-4-fluorobenzeneHCID 2733832Lithium HexamethyldisilazideHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 10797592tert-Butyl cyclopentylacetate

Product 1

HCID 68170292HCID 68170292, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent3×

Procedure

Under argon, a solution of 2.0 g (10.85 mmol) of tert-butyl cyclopentylacetate in 5 ml of abs. toluene was added dropwise to 16.3 ml of a 1 M solution, cooled to −10° C., of lithium hexamethyl-disilazide in toluene (16.3 mmol). After 10 min at −10° C., the ice bath was removed and the mixture was warmed to RT. A mixture of 2.47 g (14.1 mmol) of 1-bromo-4-fluorobenzene, 73.1 mg (0.326 mmol) of palladium(II) acetate and 269 mg (0.684 mmol) of 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl in 10 ml of abs. toluene was then added to this reaction mixture. After 1 h at RT, the reaction mixture was stirred at 80° C. overnight. 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. The crude product obtained was purified chromatographically on silica gel (mobile phase first cyclohexane, then cyclohexane/ethyl acetate 50:1). This gave 2.0 g of the title compound (61.6% of theory).

Workup

  1. customthe ice bath was removed
  2. waitAfter 1 h at RT
  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

Sources & evidence

ORD record
ord-eb257e6954d24ad5a7a4d4ddfc453a88
Source dataset
uspto-grants-2015_04
Patent number
US09018258B2

Reaction notes

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