2,2'-Bipyridine → (E)-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-(trifluoromethoxy)benzoic acid

HRID 1502966Notes

Reaction equation

HRID 1502966 reaction equation
[F:1][C:2]([F:16])([F:15])[O:3][C:4]1[CH:12]=[C:11]([CH:13]=[CH2:14])[CH:10]=[CH:9][C:5]=1[C:6]([OH:8])=[O:7].Br[CH:18]([C:23]1[CH:28]=[C:27]([Cl:29])[C:26]([F:30])=[C:25]([Cl:31])[CH:24]=1)[C:19]([F:22])([F:21])[F:20].N1C=CC=CC=1C1C=CC=CN=1>CN1CCCC1.O.[Cu]Cl>[Cl:29][C:27]1[CH:28]=[C:23]([CH:18]([C:19]([F:22])([F:21])[F:20])/[CH:14]=[CH:13]/[C:11]2[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[C:4]([O:3][C:2]([F:15])([F:16])[F:1])[CH:12]=2)[CH:24]=[C:25]([Cl:31])[C:26]=1[F:30]

Participants

7

Reactant 3

HCID 14742,2'-BipyridineHCID 866751625-(1-Bromo-2,2,2-trifluoroethyl)-1,3-dichloro-2-fluorobenzeneHCID 893063732-(Trifluoromethoxy)-4-vinylbenzoic acid

Product 1

HCID 86675151(E)-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-(trifluoromethoxy)benzoic acidYield 41.1%

Reagents, catalysts & solvents 3

HCID 62652Cuprous chlorideCatalystHCID 962WaterSolventHCID 84541-MethylpyrrolidineSolvent

Conditions

Temperature
150 °C

Procedure

To a stirred solution of 2-(trifluoromethoxy)-4-vinylbenzoic acid (0.356 g, 1.53 mmol) in 1N methyl pyrrolidine (5.0 mL) was added 1-(1-bromo-2,2,2-trifluoroethyl)-3,5-dichloro 4-fluorobenzene (1.0 g, 3.07 mmol), copper(I) chloride (CuCl; 0.03 g, 0.307 mmol) and 2,2 bipyridyl (0.095 g, 0.614 mmol). The reaction mixture was stirred at 150° C. for 1 h. After the reaction was complete by TLC, the reaction mixture was diluted with water (100 mL) and extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated under reduced pressure to obtain the crude compound which was purified by flash column chromatography to afford the product as pale yellow gummy material (0.3 g, 21%): 1H NMR (400 MHz, CDCl3) δ 8.08 (d, J=8.0 Hz, 1H), 7.45 (d, J=1.6 Hz, 1H), 7.35 (s, 3H), 6.63 (d, J=16.0 Hz, 1H), 6.50 (dd, J=16.0, 8.0 Hz, 1H), 4.15 (m, 1H); ESIMS m/z 474.81 ([M−H]−).

Workup

  1. extractionextracted with ethyl acetate (2×50 mL)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customto obtain the crude compound which
  6. customwas purified by flash column chromatography

Sources & evidence

ORD record
ord-a08ca8bd4e004f64a4b294c3e4fb3e82
Source dataset
uspto-grants-2015_12
Patent number
US09211281B2

Reaction notes

Loading…