Sodium Hydroxide → Isoquinoline, 5-chloro-6-fluoro-
Reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[N:7][CH:6]=[CH:5]2.[Cl:12]N1C(=O)CCC1=O.[OH-].[Na+]>S(=O)(=O)(O)O>[Cl:12][C:3]1[C:2]([F:1])=[CH:11][CH:10]=[C:9]2[C:4]=1[CH:5]=[CH:6][N:7]=[CH:8]2Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 50 °C
Procedure
7.0 g (38.1 mmol) 6-Fluoroisoquinoline (5) were dissolved in 60 ml concentrated sulfuric acid. At 0° C. 10.18 g N-chlorosuccinimide were added. After 1 h another 5.2 g of N-chlorosuccinimide were added and the solution was warmed to 50° C. Two more portions of 5.2 g N-chlorosuccinimide were added successively and stirring was continued at 50° C. until the reaction was complete. The reaction mixture was cooled to room temperature, poured on ice and adjusted to pH 10 by addition of sodium hydroxide. The precipitate was filtered off, taken up in dichloromethane and washed with aqueous sodium hydroxide. The organic layer was dried over magnesium sulfate, evaporated and the crude product was purified by preparative HPLC to yield 4.04 g of the desired product as trifluoroacetate. Rt=0.97 min (Method #2). Detected mass: 182.0/184.0 (M+H+).
Workup
- customAt 0° C
- customwas continued at 50° C. until the reaction
- temperatureThe reaction mixture was cooled to room temperature
- additionpoured on ice
- filtrationThe precipitate was filtered off
- washwashed with aqueous sodium hydroxide
- dry with materialThe organic layer was dried over magnesium sulfate
- customevaporated
- customthe crude product was purified by preparative HPLC
Sources & evidence
- ORD record
- ord-8a7019924d6d4ff39903911833002782
- Source dataset
- uspto-grants-2014_04
- Patent number
- US08710228B2
Reaction notes
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