Sodium hydride → 1-(3-Chloropropyl)-6,7-difluoro-3,4-dihydro-1H-quinolin-2-one

HRID 2102547Notes

Reaction equation

HRID 2102547 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[F:12])[NH:8][C:7](=[O:13])[CH2:6][CH2:5]2.[H-].[Na+].[Cl:16][CH2:17][CH2:18][CH2:19]I>CN(C=O)C>[Cl:16][CH2:17][CH2:18][CH2:19][N:8]1[C:9]2[C:4](=[CH:3][C:2]([F:1])=[C:11]([F:12])[CH:10]=2)[CH2:5][CH2:6][C:7]1=[O:13]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 813631-Chloro-3-iodopropaneHCID 148533346,7-Difluoro-3,4-dihydroquinolin-2(1h)-one

Product 1

HCID 179561691-(3-Chloropropyl)-6,7-difluoro-3,4-dihydro-1H-quinolin-2-oneYield 47.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A reaction flask was charged with 6,7-difluoro-3,4-dihydro-1H-quinolin-2-one (97KK47) (0.181 g, 0.99 mmol) in dry DMF (5 mL) under an argon atmosphere. Washed NaH (0.026 g, 1.08 mmol) was added and the mixture was stirred at rt for 0.5 h. Then 3-chloro-1-iodopropane (0.205 g, 1.00 mmol) dissolved in DMF (1 mL) was added followed by stirring at rt for 20 h. The reaction mixture was quenched with water, and the product extracted into Et2O. The combined organic layers were washed with aqueous 4% MgSO4, dried over Na2SO4, filtered, and concentrated. The product was purified by flash CC (SiO2; DCM) to give the title compound (112KK03) (0.122 g, 47%). 1H NMR (CD3OD) δ 6.99-6.86 (m, 2H), 4.03-3.99 (m, 2H), 3.60 (t, J=6.1, CH2), 2.84-2.81 (m, 2H), 2.63-2.59 (m, 2H), 2.13-2.06 (m, 2H).

Workup

  1. additionwas added
  2. stirringby stirring at rt for 20 h
  3. customThe reaction mixture was quenched with water
  4. extractionthe product extracted into Et2O
  5. washThe combined organic layers were washed with aqueous 4% MgSO4
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe product was purified by flash CC (SiO2; DCM)

Sources & evidence

ORD record
ord-d724dedb4c164faea74a25e5bf1682f4
Source dataset
uspto-grants-2009_08
Patent number
US07576078B2

Reaction notes

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