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

HRID 468744ノート

反応式

HRID 468744 の反応式
[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

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-f658c9fdfd65471798cf51cca34a70dd
出典データセット
uspto-grants-2014_01
特許番号
US08623889B2

反応ノート

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