Hydrochloric Acid → 7-Fluoro-1-methyl-1,2,3,4-tetrahydroquinolin-2-one

HRID 530337Notes

Reaction equation

HRID 530337 reaction equation
[F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][C:8](=[O:12])[NH:9]2)=[CH:4][CH:3]=1.[CH3:13]C(C)([O-])C.[K+].CI.Cl>CN(C=O)C.CCOC(C)=O>[F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][C:8](=[O:12])[N:9]2[CH3:13])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 138300Carbostyril, 3,4-dihydro-7-fluoro-HCID 23665647Potassium tert-butoxide

Product 1

HCID 224137757-Fluoro-1-methyl-1,2,3,4-tetrahydroquinolin-2-oneYield 89.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To an ice cold solution of 7-fluoro-3,4-dihydro-1H-quinolin-2-one (16.5 g, 0.1 mol) in DMF (200 mL) was added potassium tert-butoxide (22.4 g, 0.2 mol) in 2 portions. The reaction mixture was stirred at 0° C. for 30 min before MeI (25.4 g, 0.18 mol) was added. After the addition, the reaction mixture was allowed to warm up to room temperature slowly and stirred at room temperature over night. The reaction mixture was diluted with EtOAc (500 mL), then poured into 200 mL of 1 N aq. HCl. After extraction with EtOAc (200 mL, 3×), the combined organic layers were washed with brine, dried over anhy. Na2SO4, filtered and concentrated in vacuo to give crude title compounds as oil (16.0 g, 89% yield). It was used in the next step without further purification.

Workup

  1. additionwas added
  2. additionAfter the addition
  3. extractionAfter extraction with EtOAc (200 mL, 3×)
  4. washthe combined organic layers were washed with brine
  5. customdried over anhy
  6. filtrationNa2SO4, filtered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ba94da483a7a48fb92d424b6d04f48db
Source dataset
uspto-grants-2016_05
Patent number
US09353081B2

Reaction notes

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