2'-(Dicyclohexylphosphino)-N2,N2,N6,N6-tetramethyl[1,1'-biphenyl]-2,6-diamine → 2,6-Dimethyl-8-(5-(3,3,3-trifluoropropyl)quinolin-2-yl)benzofuro[2,3-b]pyridine

HRID 1056444Notes

Reaction equation

HRID 1056444 reaction equation
Cl[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([C:12]1[C:17]3[O:18][C:19]4[C:24]([C:16]=3[CH:15]=[C:14]([CH3:26])[CH:13]=1)=[CH:23][CH:22]=[C:21]([CH3:25])[N:20]=4)=[N:7]2.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(N(C)C)=CC=CC=2N(C)C)CCCCC1.[I-].[F:59][C:60]([F:65])([F:64])[CH2:61][CH2:62][Zn+]>C1COCC1.C(O[Pd]OC(=O)C)(=O)C>[CH3:25][C:21]1[N:20]=[C:19]2[O:18][C:17]3[C:12]([C:6]4[CH:5]=[CH:4][C:3]5[C:8](=[CH:9][CH:10]=[CH:11][C:2]=5[CH2:62][CH2:61][C:60]([F:65])([F:64])[F:59])[N:7]=4)=[CH:13][C:14]([CH3:26])=[CH:15][C:16]=3[C:24]2=[CH:23][CH:22]=1

Participants

6

Reactant 3

HCID 441561692'-(Dicyclohexylphosphino)-N2,N2,N6,N6-tetramethyl[1,1'-biphenyl]-2,6-diamineHCID 1184803248-(5-Chloroquinolin-2-yl)-2,6-dimethylbenzofuro[2,3-b]pyridineHCID 178506322HCID 178506322, compound

Product 1

HCID 1212668252,6-Dimethyl-8-(5-(3,3,3-trifluoropropyl)quinolin-2-yl)benzofuro[2,3-b]pyridineYield 64%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolvent

Procedure

8-(5-chloroquinolin-2-yl)-2,6-dimethylbenzofuro[2,3-b]pyridine (3.40 g, 9.48 mmol), 2′-(dicyclohexylphosphino)-N2,N2,N6,N6-tetramethyl-[1,1′-biphenyl]-2,6-diamine (0.33 g, 0.76 mmol) and diacetoxypalladium (0.09 g, 0.38 mmol) were charged into a flask and diluted with THF (150 mL). This mixture was degassed by bubbling nitrogen followed by the addition of (3,3,3-trifluoropropyl)zinc(II) iodide (40 mL, 11.8 mmol) via syringe. This mixture was stirred at room temperature overnight. Upon completion of the reaction, it was quenched with aqueous ammonium chloride then was extracted two times with 200 mL ethyl acetate. These extracts were dried over magnesium sulfate then were filtered and concentrated under vacuum. The crude residue was purified by column chromatography using 20/80 Ethyl Acetate/Heptanes. The combined fractions were triturated in Heptanes to afford 2,6-dimethyl-8-(5-(3,3,3-trifluoropropyl)quinolin-2-yl)benzofuro[2,3-b]pyridine (2.55 g, 64% yield) as an off-white powder.

Workup

  1. customThis mixture was degassed
  2. customby bubbling nitrogen
  3. customUpon completion of the reaction, it
  4. customwas quenched with aqueous ammonium chloride
  5. extractionthen was extracted two times with 200 mL ethyl acetate
  6. dry with materialThese extracts were dried over magnesium sulfate
  7. filtrationthen were filtered
  8. concentrationconcentrated under vacuum
  9. customThe crude residue was purified by column chromatography
  10. customThe combined fractions were triturated in Heptanes

Sources & evidence

ORD record
ord-8c9f9fd171fa4ddfb700178b10c32978
Source dataset
uspto-grants-2016_07
Patent number
US09397302B2

Reaction notes

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