Sodium hydride → Ethyl 8-chloro-1-oxo-1,2-dihydroisoquinoline-3-carboxylate

HRID 1476823Notes

Reaction equation

HRID 1476823 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:13]=[CH:12][CH:11]=[C:10]([CH:14]=O)[C:5]=1[C:6]([O:8]C)=O.[N+:16]([CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])#[C-]>CN(C=O)C.CCOC(C)=O>[Cl:3][C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[C:6](=[O:8])[NH:16][C:18]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[CH:14]2

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 533707Ethyl isocyanoacetateHCID 53408620Methyl 2-chloro-6-formyl-benzoate

Product 1

HCID 90386899Ethyl 8-chloro-1-oxo-1,2-dihydroisoquinoline-3-carboxylateYield 15.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
20 °C

Procedure

To a solution of NaH (652.8 mg, 16.32 mmol) in DMF (20 mL) was added methyl 2-chloro-6-formylbenzoate (2.7 g, 13.6 mmol) and ethyl 2-isocyanoacetate (1.55 g, 13.6 mmol) in DMF (5 mL) at 40° C. over a 20 minute period. The reaction mixture was stirred at 20° C. for an additional 30 minutes. The reaction mixture was subsequently diluted with EtOAc (100 mL) and washed with saturated aqueous Na2CO3. The organic phase was concentrated in vacuo. The crude product was purified by column chromatography eluting with a gradient of EtOAc (0-90%) and PE to give the title compound (0.5 g, 15.6%). ESI-MS m/z [M+H]+ 252.1.

Workup

  1. washwashed with saturated aqueous Na2CO3
  2. concentrationThe organic phase was concentrated in vacuo
  3. customThe crude product was purified by column chromatography
  4. washeluting with a gradient of EtOAc (0-90%) and PE

Sources & evidence

ORD record
ord-0440bd35943b449096a6b089816df378
Source dataset
uspto-grants-2016_08
Patent number
US09402841B2

Reaction notes

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