Potassium Hydroxide → 8-Fluoro-1-oxo-1,2-dihydroisoquinoline-3-carboxylic acid

HRID 1476811Notes

Reaction equation

HRID 1476811 reaction equation
[F:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8](/[CH:12]=[C:13]2\[N:14]=C(C3C=CC=CC=3)[O:16][C:17]\2=[O:18])[C:3]=1[C:4](OC)=[O:5].[OH-].[K+]>C(OC(=O)C)(=O)C>[F:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4](=[O:5])[NH:14][C:13]([C:17]([OH:16])=[O:18])=[CH:12]2

Participants

4

Reactant 2

HCID 14797Potassium HydroxideHCID 90387079(Z)-methyl 2-fluoro-6-((5-oxo-2-phenyloxazol-4(5H)-ylidene)methyl)benzoate

Product 1

HCID 903871878-Fluoro-1-oxo-1,2-dihydroisoquinoline-3-carboxylic acidYield 41.9%

Reagents, catalysts & solvents 1

HCID 7918Acetic AnhydrideSolvent

Procedure

A solution of crude (Z)-methyl 2-fluoro-6-((5-oxo-2-phenyloxazol-4(5H)-ylidene)methyl)benzoate (15 g) and potassium hydroxide (2.58 g, 46 mmol) in acetic anhydride (150 mL) was heated at 100° C. for 2 hours. The solvent was removed in vacuo, and the residue was diluted with water (30 mL). The resulting mixture was neutralized with 1M aqueous HCl (100 mL) and filtered. The solids were dried in vacuo to give 8-fluoro-1-oxo-1,2-dihydroisoquinoline-3-carboxylic acid (4 g, ESI-MS m/z [M+H]+ 208.0) which was converted to the methyl ester as described, below. The filtrate was concentrated under reduced pressure to give crude product which was purified by column chromatography eluting with a gradient of EtOAc (30-100%) and PE to give a first batch of the title compound (2 g, 19.6%). ESI-MS m/z [M+H]+=222.1.

Workup

  1. customThe solvent was removed in vacuo
  2. additionthe residue was diluted with water (30 mL)
  3. filtrationfiltered
  4. customThe solids were dried in vacuo

Sources & evidence

ORD record
ord-e6a5362e53c34fdca6ec09ab17b4b5e3
Source dataset
uspto-grants-2016_08
Patent number
US09402841B2

Reaction notes

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