Benzyl Bromide → 1-Benzyloxy-7-chloro-6-fluoro-isoquinoline

HRID 402521Notes

Reaction equation

HRID 402521 reaction equation
[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][NH:8][C:9]2=[O:12])=[CH:4][C:3]=1[F:13].[CH2:14](Br)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Ag+2]>[CH2:14]([O:12][C:9]1[C:10]2[C:5](=[CH:4][C:3]([F:13])=[C:2]([Cl:1])[CH:11]=2)[CH:6]=[CH:7][N:8]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

5

Reactant 2

HCID 7498Benzyl BromideHCID 598182487-Chloro-6-fluoroisoquinolin-1(2H)-one

Product 1

HCID 598182521-Benzyloxy-7-chloro-6-fluoro-isoquinolineYield 54.2%

Reagents, catalysts & solvents 2

HCID 178418647HCID 178418647, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

14.74 g (74.6 mmol) of 7-chloro-6-fluoro-2H-isoquinolin-1-one (7) were dissolved in 150 ml of toluene. After addition of 30.86 g (111.9 mmol) of silver carbonate and 15.31 g (89.5 mmol) of benzyl bromide, the mixture was stirred at 80° C. for 3 h. After cooling down to room temperature, the reaction mixture was filtered and the filtrate was evaporated. The residue was dissolved in dichloromethane and washed with water, dried with magnesium sulfate and evaporated. Final purification by preparative HPLC gave 11.63 g of the title compound. Rt=2.51 min (Method B). Detected mass: 288.1/290.1 (M+H+).

Workup

  1. temperatureAfter cooling down to room temperature
  2. filtrationthe reaction mixture was filtered
  3. customthe filtrate was evaporated
  4. dissolutionThe residue was dissolved in dichloromethane
  5. washwashed with water
  6. dry with materialdried with magnesium sulfate
  7. customevaporated
  8. customFinal purification by preparative HPLC

Sources & evidence

ORD record
ord-443867873dda4ba49a649b54c0bc50c0
Source dataset
uspto-grants-2014_06
Patent number
US08742116B2

Reaction notes

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