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

HRID 1502262노트

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HRID 1502262 반응식
[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

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-8d699cacdd2541cc861ffe732e7708cf
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09206175B2

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