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

HRID 969428
Notes
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Reaction equation

HRID 969428 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]
ParticipantsProcedureWorkupSources & evidenceReaction notes

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-one
Yield 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 IlI, 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, 1H), 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, 2 H), 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-65f83fd449044321bcdc02d155da39a5
Source dataset
uspto-grants-2007_12
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07307075B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes