Carbon Disulfide → 6-Acetyl-8-fluoro-3,4-dihydroquinolin-2(1H)-one

HRID 77437Notes

Reaction equation

HRID 77437 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[NH:10][C:9](=[O:12])[CH2:8][CH2:7]2.[C:13](Cl)(=[O:15])[CH3:14].C(=S)=S.[Cl-].[Al+3].[Cl-].[Cl-]>>[C:13]([C:4]1[CH:5]=[C:6]2[C:11](=[C:2]([F:1])[CH:3]=1)[NH:10][C:9](=[O:12])[CH2:8][CH2:7]2)(=[O:15])[CH3:14]

Participants

5

Reactant 4

HCID 6348Carbon DisulfideHCID 6367Acetyl chlorideHCID 6451240Aluminum(III) ChlorideHCID 151448738-Fluoro-1,2,3,4-tetrahydroquinolin-2-one

Product 1

HCID 100132396-Acetyl-8-fluoro-3,4-dihydroquinolin-2(1H)-oneYield 80%

Conditions

Temperature
100 °C

Procedure

To a stirring solution of 8-fluoro-3,4-dihydroquinolin-2(1H)-one (1.6 g, 9.69 mmol) and acetyl chloride (1.722 mL, 24.22 mmol) in carbon disulfide (20 mL, 9.69 mmol) at 0° C. was added in portions aluminum chloride (6.59 g, 49.4 mmol). The reaction mixture was stirred at 100° C. without a condensor until the solvent evaporated, then a condensor was fitted in place and stirring continued at 100° C. for 4 h. After cooling, the reaction contents were carefully poured into ice water and partitioned between DCM and water. The aqueous layer was extracted with DCM (3×150 mL). The combined organic washes were dried over MgSO4 and concentrated under vacuum to a tan solid. This was purified by flash chromatography on silica gel using 1% MeOH in DCM to give 6-acetyl-8-fluoro-3,4-dihydroquinolin-2(1H)-one as a yellow solid (1.6 g, 80%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.72 (br. s., 1H), 7.68-7.60 (m, 1H), 2.76-2.58 (m, 2H), 2.58-2.50 (m, 2H), 1.58 (s, 13H). LCMS: R.T.=1.335 min; [M+H]+=208.0.

Workup

  1. customevaporated
  2. customa condensor was fitted in place
  3. stirringstirring
  4. temperatureAfter cooling
  5. customthe reaction contents
  6. custompartitioned between DCM and water
  7. extractionThe aqueous layer was extracted with DCM (3×150 mL)
  8. dry with materialThe combined organic washes were dried over MgSO4
  9. concentrationconcentrated under vacuum to a tan solid
  10. customThis was purified by flash chromatography on silica gel using 1% MeOH in DCM

Sources & evidence

ORD record
ord-fd5fe9c68a9d4ee6a476bcd6db71e0cd
Source dataset
uspto-grants-2014_09
Patent number
US08841301B2

Reaction notes

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