Sodium Iodide → HCID 17956182, compound

HRID 2102619Notes

Reaction equation

HRID 2102619 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[CH3:12])[NH:8][C:7](=[O:13])[CH2:6][CH2:5]2.[H-].[Na+].Cl[CH2:17][CH2:18][CH2:19]I.[CH2:21]([CH:25]1[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1)[CH2:22][CH2:23][CH3:24].[Na+].[I-].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH2:21]([CH:25]1[CH2:30][CH2:29][N:28]([CH2:17][CH2:18][CH2:19][N:8]2[C:9]3[C:4](=[CH:3][C:2]([F:1])=[C:11]([CH3:12])[CH:10]=3)[CH2:5][CH2:6][C:7]2=[O:13])[CH2:27][CH2:26]1)[CH2:22][CH2:23][CH3:24]

Participants

8

Reactant 6

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 24758Sodium hydrideHCID 813631-Chloro-3-iodopropaneHCID 132838674-ButylpiperidineHCID 17956059HCID 17956059, compound

Product 1

HCID 17956182HCID 17956182, compoundYield 76.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A reaction flask was charged with 6-fluoro-7-methyl-3,4-dihydro-1H-quinolin-2-one (0.150 g, 0.84 mmol) in dry DMF (1 mL) under N2. NaH (60% in oil, 0.038 g, 0.92 mmol) was added and stirred at rt for 30 min. Then 3-chloro-1-iodopropane (0.131 g, 0.84 mmol) was added followed by stirring at r.t 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 (2 mL) followed by addition of 4-butylpiperidine (0.085 g, 0.6 mmol), NaI (0.150 g, 1.0 mmol), and K2CO3 (0.138 g, 1.0 mmol) and shaken at 50° C. 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 residue was purified by cation exchange CC followed by flash CC (SiO2; EtOAc) to give the title compound (107LH93-1) (0.166 g, total yield 55%). 1H NMR (CH3OD) δ 7.00 (d, J=6.4 Hz, 1H), 6.88 (d, J=9.2 Hz, 1H), 3.98-3.91 (m, 2H), 2.93-2.86 (m, 2H), 2.85-2.78 (m, 2H), 2.58-2.52 (m, 2H), 2.40-2.43 (m, 2H), 2.25 (d, J=2.0 Hz, 3H), 1.98-1.76 (m, 4H), 1.70-1.62 (m, 2H), 1.35-1.22 (m, 9H), 0.88 (t, J=7.0 Hz, 3H); 13C NMR (CH3OD) δ 171.1, 157.2 (d, J=241 Hz), 135.1 (d, J=3 Hz), 126.5 (d, J=8 Hz), 123.2 (d, J=18 Hz), 118.1 (d, J=5 Hz), 114.3 (d, J=24 Hz), 55.8, 43.9, 40.4, 36.2, 35.7, 32.0, 31.5, 29.0, 24.6, 24.3, 22.8, 13.4 (br).

Workup

  1. stirringby stirring at r.t 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 (2 mL)
  8. stirringshaken at 50° C. for 20 h
  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 residue was purified by cation exchange CC

Sources & evidence

ORD record
ord-ad7430aac65d4aae90f66e6afdd6ce9d
Source dataset
uspto-grants-2009_08
Patent number
US07576078B2

Reaction notes

Loading…