1-Bromo-3-chloropropane → 1-[3-(4-Butylpiperidin-1-yl)propyl]-7-fluoro-1h-quinolin-2-one

HRID 2102632Notes

Reaction equation

HRID 2102632 reaction equation
[F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8](=[O:12])[NH:9]2)=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:16][CH2:17][CH2:18]Cl.C([O-])([O-])=O.[K+].[K+].[CH2:26]([CH:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1)[CH2:27][CH2:28][CH3:29]>CCOCC.O.CCOC(C)=O.CN(C=O)C>[CH2:26]([CH:30]1[CH2:35][CH2:34][N:33]([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)[CH:6]=[CH:7][C:8]2=[O:12])[CH2:32][CH2:31]1)[CH2:27][CH2:28][CH3:29]

Participants

10

Reactant 5

HCID 80061-Bromo-3-chloropropaneHCID 11430Potassium CarbonateHCID 24758Sodium hydrideHCID 132838674-ButylpiperidineHCID 190675757-Fluoroquinolin-2(1H)-one

Product 1

HCID 179561101-[3-(4-Butylpiperidin-1-yl)propyl]-7-fluoro-1h-quinolin-2-oneYield 11%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A 4 mL vial was charged with 7-fluoro-1H-quinolin-2-one (0.032 g, 0.19 mmol), NaH (60% in oil, 8.7 mg, 0.21 mmol) and dry DMF (2.5 mL). The mixture was shaken at rt for 1 h and then 1-bromo-3-chloropropane (20 μl, 0.19 mmol) was added and the reaction was shaken overnight shaken at rt overnight. The mixture was then diluted with ether (25 mL) and washed water (15 mL), the ether phase was washed with water (15 mL) and brine (15 mL). The organic phase was dried over Na2SO4, and concentrated under reduced pressure. The oily residue was diluted with CH3CN (2 mL) and to the resulting solution was added: KI (0.050 g, 0.30 mmol), K2CO3 (0.041 g, 0.30 mmol) and 4-butylpiperidine (0.028 g, 0.20 mmol). The mixture was shaken at 50° C. for 72 h and then poured onto The compound EtOAc (25 mL) and water (15 mL). The water phase was extracted (2×25 mL) and the combined organic phase was dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by flash CC (SiO2; EtOAc/MeOH 4:1) followed by prep RP-HPLC to give the title compound (7.0 mg, 11%). 1H NMR (CD3OD) δ 7.89 (d, J=9.6 Hz, 1H), 7.73 (dd, J=6.2, 8.6 Hz, 111), 7.47 (dd, J=2.4, 11.6 Hz, 1H), 7.08 (dt, J=2.4, 8.6 Hz, 1H), 6.60 (d J=9.6 Hz, 1H), 4.33 (t, J=7.6 Hz, 2H), 2.98-2.00 (m, 2H), 2.50-2.42 (m, 2H), 2.05-1.86 (m, 4H), 1.55-1.64 (m, 2H), 1.36-1.15 (m, 9H), 0.90 (t, J=6.8 Hz); 13C NMR (CD3OD) δ 164.7 (d, J=248), 163.2, 140.9 (br), 139.9, 131.4 (d, J=10 Hz), 119.3 (d, J=3 Hz), 118.1 (br), 110.6 (d, J=23 Hz), 101.6 (d, J=28 Hz), 55.5, 53.9, 41.0, 36.8, 35.6, 31.9, 28.9, 24.5, 22.7, 13.2; HPLC-MS (ammonium acetate) [M+H]+=345.3

Workup

  1. stirringthe reaction was shaken overnight
  2. stirringshaken at rt overnight
  3. washwashed water (15 mL)
  4. washthe ether phase was washed with water (15 mL) and brine (15 mL)
  5. dry with materialThe organic phase was dried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. additionThe oily residue was diluted with CH3CN (2 mL) and to the resulting solution
  8. additionwas added
  9. stirringThe mixture was shaken at 50° C. for 72 h
  10. extractionThe water phase was extracted (2×25 mL)
  11. dry with materialthe combined organic phase was dried over Na2SO4
  12. concentrationconcentrated under reduced pressure
  13. customThe residue was purified by flash CC (SiO2; EtOAc/MeOH 4:1)

Sources & evidence

ORD record
ord-520b1f8857fe4e2ebdfcd1093d8ce11b
Source dataset
uspto-grants-2009_08
Patent number
US07576078B2

Reaction notes

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