Acetic Acid → Ethyl 7-chloro-1-oxo-1,2-dihydroisoquinoline-3-carboxylate

HRID 1476817Notes

Reaction equation

HRID 1476817 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:5]=[CH:6][C:7]([CH:14]=O)=[C:8]([CH:13]=1)[C:9]([O:11]C)=O.[N+:16]([CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])#[C-].C(O)(=O)C>CN(C=O)C>[Cl:3][C:4]1[CH:13]=[C:8]2[C:7]([CH:14]=[C:18]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[NH:16][C:9]2=[O:11])=[CH:6][CH:5]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 24758Sodium hydrideHCID 533707Ethyl isocyanoacetateHCID 58437623Methyl 5-chloro-2-formylbenzoate

Product 1

HCID 90386855Ethyl 7-chloro-1-oxo-1,2-dihydroisoquinoline-3-carboxylateYield 31.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
20 °C

Procedure

To a stirred mixture of NaH (1.81 g, 30.3 mmol) in DMF (20 mL) was added a solution of methyl 5-chloro-2-formylbenzoate (5.0 g, 25 mmol) and ethyl 2-isocyanoacetate (2.85 g, 25 mmol) in DMF (60 mL) at 40° C. over a 20 minute period. The reaction mixture was stirred at 20° C. for 2 hours. Its pH was adjusted to 7.0 with acetic acid (10%) and the mixture was extracted with DCM (3×200 mL). The organic layers were combined, washed with brine (200 mL), dried over Na2SO4, and concentrated. The crude product was purified by silica gel column chromatography eluting with petroleum ether and ethyl acetate (PE/EtOAc=15:1-5:1 gradient) to give the title compound (2.0 g, 31%). ESI-MS m/z [M+H]+252.1.

Workup

  1. extractionthe mixture was extracted with DCM (3×200 mL)
  2. washwashed with brine (200 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customThe crude product was purified by silica gel column chromatography
  6. washeluting with petroleum ether and ethyl acetate (PE/EtOAc=15:1-5:1 gradient)

Sources & evidence

ORD record
ord-02530edde588415687a8ebb6df7b5fc2
Source dataset
uspto-grants-2016_08
Patent number
US09402841B2

Reaction notes

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