Sodium Iodide → HCID 17956173, compound

HRID 1191457Notes

Reaction equation

HRID 1191457 reaction equation
[F:1][C:2]1[C:3]([CH3:13])=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH2:6][CH2:5]2.[H-].[Na+].Cl[CH2:17][CH2:18][CH2:19]I.[CH2:21]([O:24][CH:25]1[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1)[CH2:22][CH3:23].[Na+].[I-].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[F:1][C:2]1[C:3]([CH3:13])=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH2:17][CH2:18][CH2:19][N:28]1[CH2:29][CH2:30][CH:25]([O:24][CH2:21][CH2:22][CH3:23])[CH2:26][CH2:27]1)[C:7](=[O:12])[CH2:6][CH2:5]2

Participants

8

Reactant 6

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 24758Sodium hydrideHCID 813631-Chloro-3-iodopropaneHCID 114920374-PropoxypiperidineHCID 17956107HCID 17956107, compound

Product 1

HCID 17956173HCID 17956173, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A reaction flask was charged with 6-fluoro-5-methyl-3,4-dihydro-1H-quinolin-2-one (0.090 g, 0.50 mmol) in dry DMF (0.5 mL) under N2. NaH (60% in oil, 0.023 g, 0.55 mmol) was added and stirred at rt for 30 min. Then 3-chloro-1-iodopropane (0.079 g, 0.50 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-propoxypiperidine (0.086 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 (107LH95-2) (0.074 g, total yield 41%). 1H NMR (CH3OD) δ 7.03 (dd, J=4.8, 9.2 Hz, 1H), 6.99-6.92 (m, 1H), 3.98 (brt, J=7.4 Hz, 2H), 3.46-3.38 (m, 3H), 2.95-2.84 (m, 4H), 2.64-2.42 (m, 6H), 2.20 (d, J=2.0 Hz, 3H), 1.98-1.83 (m, 4H), 1.72-1.30 (m, 4H), 0.92 (t, J=7.4 Hz, 3H); 13C NMR (CH3OD) δ 171.1, 157.7 (d, J=240 Hz), 135.4 (d, J=3 Hz), 128.1 (d, J=4 Hz), 122.8 (d, J=18 Hz), 114.1, (d, J=9 Hz), 113.0 (d, J=25 Hz), 73.1, 69.7, 55.0, 50.3, 40.3, 30.8, 29.9, 23.9, 23.1, 22.7, 21.4, 9.8 (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-ced7e0ddf3004d3d98523e1537cd074f
Source dataset
uspto-grants-2014_03
Patent number
US08680115B2

Reaction notes

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