Toluene → 2-Methyl-4-{(E)-2-[5-(3-trifluoromethyl phenyl)pyridin-2-yl]vinyl}octahydropyrrolo[3,4-a]indolizine-1,3-dione

HRID 540642Notes

Reaction equation

HRID 540642 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5](/[CH:8]=[CH:9]/[CH:10]2[N:18]3[CH:13]([CH2:14][CH2:15][CH2:16][CH2:17]3)[CH:12]3[C:19](=[O:24])[N:20]([CH3:23])[C:21](=[O:22])[CH:11]23)=[N:6][CH:7]=1.[F:25][C:26]([F:37])([F:36])[C:27]1[CH:28]=[C:29](B(O)O)[CH:30]=[CH:31][CH:32]=1.C(=O)([O-])[O-].[K+].[K+].C1(C)C=CC=CC=1>O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(O)C>[CH3:23][N:20]1[C:21](=[O:22])[CH:11]2[CH:10](/[CH:9]=[CH:8]/[C:5]3[CH:4]=[CH:3][C:2]([C:31]4[CH:30]=[CH:29][CH:28]=[C:27]([C:26]([F:37])([F:36])[F:25])[CH:32]=4)=[CH:7][N:6]=3)[N:18]3[CH:13]([CH:12]2[C:19]1=[O:24])[CH2:14][CH2:15][CH2:16][CH2:17]3

Participants

8

Reactant 4

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 27343883-(Trifluoromethyl)phenylboronic acidHCID 534923684-[(E)-2-(5-bromopyridin-2-yl)vinyl]-2-methyloctahydropyrrolo[3,4-a]-indolizine-1,3-dione2×

Product 1

HCID 534925042-Methyl-4-{(E)-2-[5-(3-trifluoromethyl phenyl)pyridin-2-yl]vinyl}octahydropyrrolo[3,4-a]indolizine-1,3-dione

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
100 °C

Procedure

A mixture consisting of 42 mg of 4-[(E)-2-(5-bromopyridin-2-yl)vinyl]-2-methyloctahydropyrrolo[3,4-a]indolizine-1,3-dione (from Example 6, racemic mixture 1), 2.5 mg of tetrakis(triphenylphosphine)palladium(0), 25 mg of 3-trifluoromethylphenylboronic acid, 37 mg of potassium carbonate, 1.5 ml of toluene, 0.3 ml of ethanol and 0.75 ml of water is stirred at 100° C. for 5 h. After cooling, the mixture is taken up in 20 ml of water and the product is extracted by shaking with 20 ml of ethyl acetate. After drying and concentration of the organic phase, an oil is obtained. The crude product is purified by column chromatography (silica gel, MeOH:DCM=1:99).

Workup

  1. temperatureAfter cooling
  2. extractionthe product is extracted
  3. stirringby shaking with 20 ml of ethyl acetate
  4. customAfter drying
  5. customconcentration of the organic phase, an oil is obtained
  6. customThe crude product is purified by column chromatography (silica gel, MeOH:DCM=1:99)

Sources & evidence

ORD record
ord-c03b55e0e8994cbd9c671a03778f8265
Source dataset
uspto-grants-2014_10
Patent number
US08871798B2

Reaction notes

Loading…