Isoquinoline, 1-chloro- → HCID 57938388, compound

HRID 539477Notes

Reaction equation

HRID 539477 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][N:3]=1.[CH3:12][O:13][C:14]1[CH:15]=[C:16](B(O)O)[CH:17]=[CH:18][CH:19]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.O.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O.C1(C)C=CC=CC=1>[CH3:12][O:13][C:14]1[CH:19]=[C:18]([C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[CH:5]=[CH:4][N:3]=2)[CH:17]=[CH:16][CH:15]=1

Participants

7

Reactant 4

HCID 140539Isoquinoline, 1-chloro-HCID 2734370(3-Methoxyphenyl)boronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 22031701Potassium phosphate, tribasic, monohydrate

Product 1

HCID 57938388HCID 57938388, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

1-chloroisoquinoline (7 g, 42.8 mmol), (3-methoxyphenyl)boronic acid (8.78 g, 57.8 mmol), Tris(dibenzylideneacetone)palladium(0) (0.783 g, 0.856 mmol) and 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (S-Phos) (1.403 g, 3.42 mmol) were charged into the reaction vessel with 250 mL of toluene. Lastly, potassium phosphate tribasic monohydrate (29.5 g, 128 mmol) was dissolved in 60 mL of water and was charged into the reaction mixture. The reaction was degassed with nitrogen gas then was heated to reflux for 18 h. The reaction mixture was cooled to room temperature and the toluene layer was separated and dried over magnesium sulfate. The organics were filtered and stripped under vacuum. The crude residue was purified by silica gel chromatography using 25-35% ethyl acetate/hexanes yielding 9.4 g (93%) of 1-(3-methoxyphenyl)isoquinoline as a viscous yellow oil.

Workup

  1. additionwas charged into the reaction mixture
  2. customThe reaction was degassed with nitrogen gas
  3. temperaturethen was heated
  4. temperatureto reflux for 18 h
  5. customthe toluene layer was separated
  6. dry with materialdried over magnesium sulfate
  7. filtrationThe organics were filtered
  8. customThe crude residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-f24a20f5b1774badada08a209fae8866
Source dataset
uspto-grants-2014_10
Patent number
US08871361B2

Reaction notes

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