Isoamyl Nitrite → 5,8-dichloro-7-methoxy-3,4-dihydroisoquinolin-1(2H)-one

HRID 577490Notes

Reaction equation

HRID 577490 reaction equation
N(OCCC(C)C)=O.[Cl-:9].[Li+].N[C:12]1[C:13]([O:24][CH3:25])=[CH:14][C:15]([Cl:23])=[C:16]2[C:21]=1[C:20](=[O:22])[NH:19][CH2:18][CH2:17]2>C(#N)C.[Cu](Cl)Cl>[Cl:23][C:15]1[CH:14]=[C:13]([O:24][CH3:25])[C:12]([Cl:9])=[C:21]2[C:16]=1[CH2:17][CH2:18][NH:19][C:20]2=[O:22]

Participants

6

Reactant 3

HCID 8053Isoamyl NitriteHCID 433294Lithium ChlorideHCID 867237158-amino-5-chloro-7-methoxy-3,4-dihydroisoquinolin-1(2H)-one

Product 1

HCID 867237165,8-dichloro-7-methoxy-3,4-dihydroisoquinolin-1(2H)-oneYield 92%

Reagents, catalysts & solvents 2

HCID 24014Cupric ChlorideCatalystHCID 6342AcetonitrileSolvent

Procedure

Isopentyl nitrite (20 mL, 0.149 mol) was added dropwise to a heated (55° C.) suspension of copper (II) chloride (40 g, 0.298 mol) and lithium chloride (38 g, 0.905 mol) in acetonitrile (500 mL). The mixture was stirred at that temperature for 5 minutes, then 8-amino-5-chloro-7-methoxy-3,4-dihydroisoquinolin-1(2H)-one (296d, 20 g, 0.089 mol) was added in portions. After the addition was complete, stirring was continued at 55° C. for 45 minutes. The reaction mixture was cooled to room temperature, quenched with saturated aqueous ammonium chloride (300 mL), and extracted with ethyl acetate (4×200 mL). The combined organic layers were washed with aqueous ammonium chloride (200 mL) and brine (100 mL), dried over sodium sulfate, and concentrated under vacuum to give crude 5,8-dichloro-7-methoxy-3,4-dihydroisoquinolin-1(2H)-one (296e, 20 g, 90% purity, 92% yield) as a brown solid. MS: 245 [M+1].

Workup

  1. temperaturea heated
  2. additionAfter the addition
  3. stirringstirring
  4. waitwas continued at 55° C. for 45 minutes
  5. customquenched with saturated aqueous ammonium chloride (300 mL)
  6. extractionextracted with ethyl acetate (4×200 mL)
  7. washThe combined organic layers were washed with aqueous ammonium chloride (200 mL) and brine (100 mL)
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-4c2bc8d868214b2aa6db96c32bcb9061
Source dataset
uspto-grants-2015_05
Patent number
US09040515B2

Reaction notes

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