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) of 6-Fluoroisoquinoline (23) are dissolved in 60 mL of concentrated sulfuric acid. At 0° C. 10.18 g of N-Chlorosuccinimide are added. After 1 h another 5.2 g of N-Chlorosuccinimide are added and the solution is warmed to 50° C. Two more portions of 5.2 g N-Chlorosuccinimide are added successively and stirring is continued at 50° C. until the reaction is complete. The reaction mixture is cooled to room temperature, is poured on ice and adjusted to pH 10 by addition of sodium hydroxide. The precipitate is filtered off, taken up in dichloromethane and washed with aqueous sodium hydroxide. The organic layer is dried over magnesium sulfate, evaporated and the crude product is purified by preparative HPLC to yield 4.04 g of 5-Chlor-6-fluor-isoquinoline (151) as trifluoroacetate. Rt=0.97 min (Method #2). Detected mass: 182.0/184.0 (M+H+).
Workup
- customAt 0° C
- customis continued at 50° C. until the reaction
- temperatureThe reaction mixture is cooled to room temperature
- additionis poured on ice
- filtrationThe precipitate is filtered off
- washwashed with aqueous sodium hydroxide
- dry with materialThe organic layer is dried over magnesium sulfate
- customevaporated
- customthe crude product is purified by preparative HPLC
Sources & evidence
- ORD record
- ord-ac3e09ea33dc4782b85e3d7e18e8ef6a
- Source dataset
- uspto-grants-2013_08
- Patent number
- US08501736B2
Reaction notes
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