Hydrochloric Acid → HCID 17956059, compound

HRID 1191342Notes

Reaction equation

HRID 1191342 reaction equation
Cl[CH2:2][CH2:3][C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([F:13])=[C:9]([CH3:14])[CH:8]=1)=[O:5].ClCCC(Cl)=O.C([O-])([O-])=O.[K+].[K+].[Al+3].[Cl-].[Cl-].[Cl-].Cl>CCOC(C)=O.CC#N>[F:13][C:10]1[CH:11]=[C:12]2[C:7](=[CH:8][C:9]=1[CH3:14])[NH:6][C:4](=[O:5])[CH2:3][CH2:2]2.[F:13][C:10]1[C:9]([CH3:14])=[C:8]2[C:7](=[CH:12][CH:11]=1)[NH:6][C:4](=[O:5])[CH2:3][CH2:2]2

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 693643-Chloropropionyl chlorideHCID 6451240Aluminum(III) ChlorideHCID 17956097HCID 17956097, compound

Product 2

HCID 17956059HCID 17956059, compoundYield 14%HCID 17956107HCID 17956107, compoundYield 4%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-Chloro-N-(4-fluoro-3-methyl-phenyl)-propionamide (3.8 g, 30 mmol), 3-chloropropionyl chloride (2.9 mL, 30 mmol) and K2CO3 (5.0 g, 36 mmol) were added to CH3CN (50 mL) and the mixture was stirred for 44 h at rt. Thereafter, the reaction was diluted with EtOAc (50 mL) and washed with water (20 mL), HCl (20 mL, 4N) and brine (20 mL). The organic phase was dried with Na2SO4, filtered and concentrated under reduced pressure. The residue (5.9 g) was heated to 135° C. and small portions of AlCl3 (11 g, 82 mmol) were added during 30 min, the reaction was then cooled to 50° C. and HCl (4N 20, mL) was added and the resulting mixture was stirred for 15 min. The mixture was extracted with EtOAc (50 mL) and the organic phase was washed with water (20 mL). The resulting organic phase was dried (Na2SO4), filtered concentrated under reduced pressure and purified by prep HPLC to yield 6-fluoro-7-methyl-3,4-dihydro-1H-quinolin-2-one (0.76 g, 14%) and 6-fluoro-5-methyl-3,4-dihydro-1H-quinolin-2-one (0.190 g, 4%). 6-Fluoro-7-methyl-3,4-dihydro-1H-quinolin-2-one (107LH75-1). 1H NMR (CDCl3) δ 8.86 (brs, 8.86, 1H), 6.81 (d, J=9.2 Hz, 1H), 6.62 (d, J=6.8 Hz, 1H), 2.91 (brt, J=7.6 Hz, 3H), 2.94-2.87 (m, 2H), 2.20 (d, J=2.0 Hz). 6-Fluoro-5-methyl-3,4-dihydro-1H-quinolin-2-one (107LH75-2). 1H NMR (CDCl3) δ 8.78 (brs, 1H), 6.85 (t, J=8.8 Hz, 1H), 6.62 (dd, J=4.5, 8.8 Hz, 1H), 2.92 (brt, J=7.6 Hz, 2H), 2.64-2.58 (m, 2H), 2.20 (d, J=2.4 Hz, 3H).

Workup

  1. washwashed with water (20 mL), HCl (20 mL, 4N) and brine (20 mL)
  2. dry with materialThe organic phase was dried with Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. temperatureThe residue (5.9 g) was heated to 135° C.
  6. temperaturethe reaction was then cooled to 50° C.
  7. stirringthe resulting mixture was stirred for 15 min
  8. extractionThe mixture was extracted with EtOAc (50 mL)
  9. washthe organic phase was washed with water (20 mL)
  10. dry with materialThe resulting organic phase was dried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. custompurified by prep HPLC

Sources & evidence

ORD record
ord-c002816a9bf9482084b19cc33afab80e
Source dataset
uspto-grants-2014_03
Patent number
US08680115B2

Reaction notes

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