Chloroform → 3-Chloro-7-(5-fluoro-2-methylphenyl)isoquinoline

HRID 468744Notes

Reaction equation

HRID 468744 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:19])=[C:6]([C:8]2[CH:17]=[C:16]3[C:11]([CH:12]=[C:13](N)[N:14]=[CH:15]3)=[CH:10][CH:9]=2)[CH:7]=1.C(Cl)(Cl)[Cl:21].N(OC(C)(C)C)=O.C([O-])([O-])=O.[Na+].[Na+]>C(OCC)(=O)C>[Cl:21][C:13]1[N:14]=[CH:15][C:16]2[C:11]([CH:12]=1)=[CH:10][CH:9]=[C:8]([C:6]1[CH:7]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=1[CH3:19])[CH:17]=2

Participants

6

Reactant 4

HCID 6212ChloroformHCID 10340Sodium CarbonateHCID 10906Tert-Butyl nitriteHCID 574102447-(5-Fluoro-2-methylphenyl)isoquinolin-3-amine

Product 1

HCID 866749363-Chloro-7-(5-fluoro-2-methylphenyl)isoquinolineYield 36.3%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 7-(5-fluoro-2-methylphenyl)isoquinolin-3-amine (0.5177 g, 2.052 mmol) in chloroform (10 mL, 100 mmol) was added cuprous monochloride (0.3159 g, 3.191 mmol) and tert-butyl nitrite (0.50 mL, 3.8 mmol). The reaction mixture was stirred at room temperature in a flask shielded from the light with foil for 20 hours. To the reaction mixture was added 2M aqueous Na2CO3 and ethyl acetate, and the resulting mixture was filtered through celite. The organic layer was then dried over MgSO4, filtered, and evaporated in vacuo. The resulting residue was purified via flash chromatography on silica gel (40 g silica, solvent gradient: 0-50% ethyl acetate in heptanes) to yield 202.6 mg (36%) of 3-chloro-7-(5-fluoro-2-methylphenyl)isoquinoline. LCMS (ESI): M+H=272.2; 1H NMR (400 MHz, DMSO-d6) δ 9.26 (s, 1H), 8.19 (s, 1H), 8.11 (s, 1H), 8.05 (d, J=8.5 Hz, 1H), 7.87 (d, J=8.5 Hz, 1H), 7.45-7.36 (m, 1H), 7.19 (t, J=7.9 Hz, 2H), 2.24 (s, 3H).

Workup

  1. filtrationthe resulting mixture was filtered through celite
  2. dry with materialThe organic layer was then dried over MgSO4
  3. filtrationfiltered
  4. customevaporated in vacuo
  5. customThe resulting residue was purified via flash chromatography on silica gel (40 g silica, solvent gradient: 0-50% ethyl acetate in heptanes)

Sources & evidence

ORD record
ord-f658c9fdfd65471798cf51cca34a70dd
Source dataset
uspto-grants-2014_01
Patent number
US08623889B2

Reaction notes

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