2,2'-Bipyridine → (E)-tert-butyl-5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)indoline-1-carboxylate

HRID 1503526Notes

Reaction equation

HRID 1503526 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([CH:17]=[CH2:18])=[CH:14][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[CH:20]([C:25]1[CH:26]=[C:27]([Cl:33])[C:28]([F:32])=[C:29]([Cl:31])[CH:30]=1)[C:21]([F:24])([F:23])[F:22].N1C=CC=CC=1C1C=CC=CN=1>ClC1C=CC=CC=1Cl.Cl[Cu]>[Cl:31][C:29]1[CH:30]=[C:25]([CH:20]([C:21]([F:24])([F:23])[F:22])/[CH:18]=[CH:17]/[C:13]2[CH:12]=[C:11]3[C:16](=[CH:15][CH:14]=2)[N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][CH2:10]3)[CH:26]=[C:27]([Cl:33])[C:28]=1[F:32]

Participants

6

Reactant 3

HCID 14742,2'-BipyridineHCID 86675161tert-Butyl 5-vinylindoline-1-carboxylateHCID 866751625-(1-Bromo-2,2,2-trifluoroethyl)-1,3-dichloro-2-fluorobenzene

Product 1

HCID 86675160(E)-tert-butyl-5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)indoline-1-carboxylateYield 61%

Reagents, catalysts & solvents 2

HCID 62652Cuprous chlorideCatalystHCID 72391,2-DichlorobenzeneSolvent

Conditions

Temperature
150 °C

Procedure

To a stirred solution of tert-butyl-5-vinylindoline-1-carboxylate (1.28 g, 5.23 mmol) in 1,2-dichlorobenzene (10.0 mL), was added 5-(1-bromo-2,2,2-trifluoroethyl)-1,3-dichloro-2-fluorobenzene (3.4 g, 10 mmol), CuCl (103 mg, 1.05 mmol) and 2,2-bipyridyl (0.326 g, 2.092 mmol) and the resultant reaction mixture was degassed with argon for 30 min and heated to 150° C. for 1 h. The reaction mixture was cooled to RT and filtered and the filtrate was concentrated under reduced pressure. The crude compound was purified by column chromatography (SiO2, 100-200 mesh; 2% ethyl acetate/petroleum ether) to afford the title compound as a pale yellow gummy solid (0.3 g, 61%): 1H NMR (400 MHz, CDCl3) δ 7.34 (d, J=6.0 Hz, 2H), 7.22 (s, 2H), 7.16 (d, J=8.4 Hz, 1H), 6.52 (d, J=16.0 Hz, 1H), 6.21 (dd, J=16.0, 7.6 Hz, 1H), 4.07 (m, 3H), 3.10 (t, J=8.4 Hz, 2H), 1.55 (s, 9H); ESIMS m/z 433.79 ([M−H]−); IR (thin film) 1168, 858 cm−1.

Workup

  1. customthe resultant reaction mixture
  2. customwas degassed with argon for 30 min
  3. temperatureThe reaction mixture was cooled to RT
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe crude compound was purified by column chromatography (SiO2, 100-200 mesh; 2% ethyl acetate/petroleum ether)

Sources & evidence

ORD record
ord-a119bf2659d84ed59d497b33da8683ab
Source dataset
uspto-grants-2015_12
Patent number
US09212163B2

Reaction notes

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