Acetone → 5-fluoro-2-methyl-8-nitro-3,4-dihydro-2H-isoquinolin-1-one

HRID 604274Notes

Reaction equation

HRID 604274 reaction equation
[CH3:1][O:2][C:3](=[O:17])[C:4]1[C:9]([N+:10]([O-:12])=[O:11])=[CH:8][CH:7]=[C:6]([F:13])[C:5]=1[CH2:14][CH2:15]O.[Na].[Br-].[Na+].Cl[N:22]1C(=[O:28])N(Cl)C(=O)N(Cl)[C:23]1=O.C[C:34](C)=[O:35]>CC1(C)N([O])C(C)(C)CCC1.C(O)(C)C>[F:13][C:6]1[CH:7]=[CH:8][C:9]([N+:10]([O-:12])=[O:11])=[C:4]2[C:5]=1[CH2:14][CH2:15][N:22]([CH3:23])[C:3]2=[O:2].[CH3:1][O:2][C:3](=[O:17])[C:4]1[C:9]([N+:10]([O-:12])=[O:11])=[CH:8][CH:7]=[C:6]([F:13])[C:5]=1[CH2:14][CH2:15][C:34]([OH:35])=[O:28]

Participants

9

Reactant 5

HCID 180AcetoneHCID 6909Trichloroisocyanuric AcidHCID 253881Sodium BromideHCID 5360545SodiumHCID 670377633-Fluoro-2-(2-hydroxyethyl)-6-nitro-benzoic acid methyl ester

Product 2

HCID 598491765-fluoro-2-methyl-8-nitro-3,4-dihydro-2H-isoquinolin-1-oneHCID 598492232-(2-Carboxy-ethyl)-3-fluoro-6-nitro-benzoic acid methyl ester

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 2724126TempoSolvent

Procedure

To a solution of 3-fluoro-2-(2-hydroxyethyl)-6-nitro-benzoic acid methyl ester (51.4 g, 0.2 mol) in acetone (1000 mL), 2,2,6,6-tetramethylpiperidine 1-oxyl, Free radical, (460.6 mg, 2.95 mmol), an aqueous 15% solution of sodium hydrocarboxide (400 mL) and sodium bromide (3.02 g, 29.3 mmol) was added. Trichloroisocyanuric acid (68.4 g, 0.29 mol) was then slowly added within 30 min at rt. After completion of the addition and being stirred at rt for 2.5 hrs, 15 mL of isopropanol was added at 0° C. carefully. The mixture was concentrated under reduced pressure. The mixture was extracted three times with ethyl acetate. The organic layer was extracted three times with 1N sodium hydroxide. The combined water layer was washed once with ethyl acetate, then acidified with 5N hydrogen chloride at 0° C. After extraction four times with ethyl acetate, the organic layer was washed with water and brine, dried over magnesium sulfate, and evaporated in vacuo. The title compound 2-(2-carboxy-ethyl)-3-fluoro-6-nitro-benzoic acid methyl ester (28.7 g) was obtained as yellow solid in 72% yield (2 steps).

Workup

  1. additionAfter completion of the addition
  2. concentrationThe mixture was concentrated under reduced pressure
  3. extractionThe mixture was extracted three times with ethyl acetate
  4. extractionThe organic layer was extracted three times with 1N sodium hydroxide
  5. washThe combined water layer was washed once with ethyl acetate
  6. customacidified with 5N hydrogen chloride at 0° C
  7. extractionAfter extraction four times with ethyl acetate
  8. washthe organic layer was washed with water and brine
  9. dry with materialdried over magnesium sulfate
  10. customevaporated in vacuo

Sources & evidence

ORD record
ord-8df17495f7fa48b19ae1f44bacf93d34
Source dataset
uspto-grants-2011_03
Patent number
US07910585B2

Reaction notes

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