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Cesium fluoride → 2-[2'-(3-Methoxypropyl)-3-methylbiphenyl-4-yl]-3-pyridin-3-ylpropanenitrile

HRID 2194921
Notes
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Reaction equation

HRID 2194921 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH2:11][C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)[C:9]#[N:10])=[C:4]([CH3:18])[CH:3]=1.[CH3:19][O:20][CH2:21][CH2:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1B(O)O.[F-].[Cs+]>COCCOC.O>[CH3:19][O:20][CH2:21][CH2:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH2:11][C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)[C:9]#[N:10])=[C:4]([CH3:18])[CH:3]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 3

HCID 25953Cesium fluorideHCID 58083347[2-(3-Methoxypropyl)phenyl]boronic acidHCID 674455322-(4-Bromo-2-methylphenyl)-3-pyridin-3-ylpropanenitrile

Product 1

HCID 674474272-[2'-(3-Methoxypropyl)-3-methylbiphenyl-4-yl]-3-pyridin-3-ylpropanenitrile

Reagents, catalysts & solvents 2

HCID 962WaterSolvent
HCID 8071
1,2-Dimethoxyethane
Solvent

Procedure

To a solution 2-(4-bromo-2-methylphenyl)-3-pyridin-3-ylpropanenitrile (1 eq.) from step 1 and [2-(3-methoxypropyl)phenyl]boronic acid from EXAMPLE 3, step 1 (1.2 eq.) in DME (0.1M) at room temperature was added palladium tetrakistriphenyl phosphine (Pd(PPh3)4; 0.05 eq.) and CsF (2.4 eq.). The mixture was refluxed for 2 h, cooled to room temperature, poured in water and extracted with EtOAc. The organic extract was washed with water, brine, dried over Na2SO4 filtered and concentrated. Purification by column chromatography on silica gel (Combi-Flash by ISCO), eluting with Hex/EtOAc (0 to 65% in 30 min) afforded the desired compound.

Workup

  1. temperatureThe mixture was refluxed for 2 h
  2. extractionextracted with EtOAc
  3. extractionThe organic extract
  4. washwas washed with water, brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by column chromatography on silica gel (Combi-Flash by ISCO)
  9. washeluting with Hex/EtOAc (0 to 65% in 30 min)

Sources & evidence

ORD record
ord-56da723d34294edbb740bf37cf5679bd
Source dataset
uspto-grants-2012_12
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08334308B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes