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

HRID 45182Notes

Reaction equation

HRID 45182 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.C(OCC)(=O)C>C1COCC1.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

6

Reactant 3

HCID 7498Benzyl Bromide2×HCID 8857Ethyl AcetateHCID 598182487-Chloro-6-fluoroisoquinolin-1(2H)-one

Product 1

HCID 598182521-Benzyloxy-7-chloro-6-fluoro-isoquinoline

Reagents, catalysts & solvents 2

HCID 178418647HCID 178418647, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

7-Chloro-6-fluoro-2H-isoquinolin-1-one (prepared according to WO 2007/012422; 52.2 g) was dissolved in THF (1 L). After addition of silver carbonate (145.5 g) and benzyl bromide (40.6 mL), the mixture was stirred at room temperature overnight. Another 6.2 mL of benzyl bromide were added and the mixture was stirred at 70° C. for 2 h. After cooling down to room temperature, the reaction mixture was diluted by addition of 1 L of ethyl acetate and filtered over celite. The filter cake was washed thoroughly, the organic layer was evaporated and subjected to silica gel chromatography (n-heptanes: methyl tert. butyl ether) to give 27.8 g of the title compound (38). Rt=3.73 min (Method 1). Detected mass: 288.1 (M+H+).

Workup

  1. stirringthe mixture was stirred at 70° C. for 2 h
  2. temperatureAfter cooling down to room temperature
  3. filtrationfiltered over celite
  4. washThe filter cake was washed thoroughly
  5. customthe organic layer was evaporated

Sources & evidence

ORD record
ord-db8e1d54094c4a8cb96526c15bfc728f
Source dataset
uspto-grants-2013_09
Patent number
US08541449B2

Reaction notes

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