Dimethylformamide → 6-Bromo-2-(3-chloro-2,2-dimethylpropyl)-1-oxo-1,2-dihydroisoquinoline-4-carbaldehyde

HRID 906400Notes

Reaction equation

HRID 906400 reaction equation
P(Cl)(Cl)([Cl:3])=O.[Br:6][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[C:13](=[O:17])[N:12]([CH2:18][C:19]([CH3:30])([CH3:29])[CH2:20]O[Si](C(C)(C)C)(C)C)[CH:11]=[CH:10]2.CN([CH:34]=[O:35])C>O>[Br:6][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[C:13](=[O:17])[N:12]([CH2:18][C:19]([CH3:29])([CH3:30])[CH2:20][Cl:3])[CH:11]=[C:10]2[CH:34]=[O:35]

Participants

5

Reactant 3

HCID 6228Dimethylformamide2×HCID 24813Phosphorus oxychlorideHCID 671303156-Bromo-2-(3-{[tert-butyl(dimethyl)silyl]oxy}-2,2-dimethylpropyl)isoquinolin-1(2H)-one

Product 1

HCID 866409616-Bromo-2-(3-chloro-2,2-dimethylpropyl)-1-oxo-1,2-dihydroisoquinoline-4-carbaldehyde

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Phosphorus oxychloride (2.57 mL) was added to a cooled solution of DMF (10 mL) and the reaction stirred at room temperature for 2 h before being treated with 6-bromo-2-(3-{[tert-butyl(dimethyl)silyl]oxy}-2,2-dimethylpropyl)isoquinolin-1(2H)-one (Example 1c, 1.3 g) in DMF (10 mL) under nitrogen. The resulting solution was stirred at 70° C. for 10 h. The reaction mixture was diluted with water (300 mL), and extracted with ethyl acetate (300 mL). The organic was dried (MgSO4), filtered and evaporated to afford crude product. The crude product was purified (SiO2 chromatography, elution 50% diethyl ether in isohexane) to afford the subtitle compound (0.45 g) as a solid.

Workup

  1. stirringThe resulting solution was stirred at 70° C. for 10 h
  2. extractionextracted with ethyl acetate (300 mL)
  3. dry with materialThe organic was dried (MgSO4)
  4. filtrationfiltered
  5. customevaporated
  6. customto afford crude product
  7. customThe crude product was purified
  8. wash(SiO2 chromatography, elution 50% diethyl ether in isohexane)

Sources & evidence

ORD record
ord-29dabfda5d9c42debdbd1013728228a3
Source dataset
uspto-grants-2011_09
Patent number
US08012980B2

Reaction notes

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