Ammonia → 4-Chloroisoquinoline

HRID 10548

Reaction equation

HRID 10548 reaction equation
N[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[N:4][CH:3]=1.N([O-])=O.[Na+].N.[ClH:17]>[Cu]Cl>[Cl:17][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[N:4][CH:3]=1

Participants

6

Reactant 4

HCID 222AmmoniaHCID 313Hydrochloric Acid2×HCID 902374-AminoisoquinolineHCID 23668193Sodium Nitrite

Product 1

HCID 6409744-Chloroisoquinoline

Reagents, catalysts & solvents 1

HCID 62652Cuprous chlorideCatalyst

Procedure

Intermediate 87 (1.27 g) was dissolved in 1 N aqueous hydrochloric acid (36 ml) and added dropwise with an aqueous solution (36 ml) of sodium nitrite (1.21 g, Wako Pure Chemical Industries) with ice cooling. The obtained suspension was added dropwise to a solution of copper(I) chloride (1.83 g, Wako Pure Chemical Industries) in 1 N aqueous hydrochloric acid (20 ml) with ice cooling, then warmed to room temperature and stirred for 15 hours. The reaction mixture was added with 28% aqueous ammonia (50 ml) and extracted twice with ethyl acetate (150 ml for each time). The organic layer was dried over anhydrous sodium sulfate, and then the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=2:1) to obtain the title compound (433 mg).

Workup

  1. extractionextracted twice with ethyl acetate (150 ml for each time)
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. customthe solvent was evaporated under reduced pressure
  4. customThe residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=2:1)

Sources & evidence

ORD record
ord-6e55001f2da4432ebe9991fc4a77c3aa
Source dataset
uspto-grants-2006_08
Patent number
US07094789B2

Linked notes

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