1-Bromo-3-chloropropane → 3-(4-Butylpiperidin-1-yl)propyl-7-fluoro-3,4-dihydro-1H-quinolin-2-one

HRID 2102614Notes

Reaction equation

HRID 2102614 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.[H-].[Na+].Br[CH2:16][CH2:17][CH2:18]Cl.[CH2:20]([CH:24]1[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1)[CH2:21][CH2:22][CH3:23].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH2:20]([CH:24]1[CH2:29][CH2:28][N:27]([CH2:16][CH2:17][CH2:18][N:9]2[C:10]3[C:5](=[CH:4][CH:3]=[C:2]([F:1])[CH:11]=3)[CH2:6][CH2:7][C:8]2=[O:12])[CH2:26][CH2:25]1)[CH2:21][CH2:22][CH3:23]

Participants

7

Reactant 5

HCID 80061-Bromo-3-chloropropaneHCID 11430Potassium CarbonateHCID 24758Sodium hydrideHCID 138300Carbostyril, 3,4-dihydro-7-fluoro-HCID 132838674-Butylpiperidine

Product 1

HCID 179561583-(4-Butylpiperidin-1-yl)propyl-7-fluoro-3,4-dihydro-1H-quinolin-2-oneYield 37.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A reaction flask was charged with 7-fluoro-3,4-dihydro-1H-quinolin-2-one (97LH36) (0.080 g, 0.48 mmol) in dry DMF (2 mL) under Argon. NaH (60% in oil, 0.021 g, 0.53 mmol) was added and the mixture was stirred at rt for 0.5 h. Then 1-bromo-3-chloropropane (0.075 g, 0.48 mmol) was added followed by stirring at rt for 20 h. The reaction mixture was quenched with water, and the product extracted into EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated. The crude material was dissolved in MeCN (3 mL) followed by addition of 4-butylpiperidine (0.071 g, 0.50 mmol), KI (0.166 g, 1.00 mmol), and K2CO3 (0.138 g, 1.00 mmol) and shaken at 50° for 4 days. The reaction mixture was quenched with water, and the product extracted into EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated. The product was purified by flash CC (SiO2; EtOAc) to give the title compound (107LH21) (0.062 g, 37%). 1H NMR (CD3OD) δ 7.20-7.17 (m, 1H), 7.01-6.98 (m, 1H), 6.76-6.72 (m, 1H), 3.95 (t, J=7.4 Hz, CH2), 2.93-2.84 (m, 4H), 2.61-2.57 (m, 2H), 2.42-2.38 (m, 2H), 2.00-1.94 (m, 2H), 1.84-1.80 (m, 2H), 1.68 (d, J=10.0 Hz, 2H), 1.30-1.22 (m, 9H), 0.89 (t, J=6.8 Hz, CH3); HPLC-MS (ammonium acetate) [M+H+]=347.31.

Workup

  1. stirringby stirring at rt for 20 h
  2. customThe reaction mixture was quenched with water
  3. extractionthe product extracted into EtOAc
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. dissolutionThe crude material was dissolved in MeCN (3 mL)
  8. stirringshaken at 50° for 4 days
  9. customThe reaction mixture was quenched with water
  10. extractionthe product extracted into EtOAc
  11. dry with materialThe combined organic layers were dried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customThe product was purified by flash CC (SiO2; EtOAc)

Sources & evidence

ORD record
ord-6a03a57e82be40228a752966df60ce82
Source dataset
uspto-grants-2009_08
Patent number
US07576078B2

Reaction notes

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