1-Bromo-3-chloropropane → 1-(3-Chloropropyl)-6-fluoro-3,4-dihydro-1H-quinolin-2-one

HRID 2103202Notes

Reaction equation

HRID 2103202 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH2:6][CH2:5]2.[H-].[Na+].Br[CH2:16][CH2:17][CH2:18][Cl:19]>CN(C=O)C>[Cl:19][CH2:18][CH2:17][CH2:16][N:8]1[C:9]2[C:4](=[CH:3][C:2]([F:1])=[CH:11][CH:10]=2)[CH2:5][CH2:6][C:7]1=[O:12]

Participants

5

Reactant 3

HCID 80061-Bromo-3-chloropropaneHCID 24758Sodium hydrideHCID 136907656-Fluoro-3,4-dihydroquinolin-2(1H)-one

Product 1

HCID 179561031-(3-Chloropropyl)-6-fluoro-3,4-dihydro-1H-quinolin-2-oneYield 73.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A reaction flask was charged with 6-fluoro-3,4-dihydro-1H-quinolin-2-one (0.180 g, 1.09 mmol) in dry DMF (2 mL) under Argon. NaH (60% in oil, 0.048 g, 1.20 mmol) was added and the mixture was stirred at rt for 0.5 h. Then 1-bromo-3-chloropropane (0.180 g, 1.14 mmol) was added followed by stirring at rt 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 product was purified by flash CC (SiO2; DCM) to give the title compound (92LH79) (0.193 g, 73%). 1H NMR (CDCl3) δ 7.02-6.88 (m, 3H), 4.09-4.05 (m, 2H), 3.61 (t, J=6.3 Hz, CH2), 2.87 (t, J=6.7 Hz, CH2), 2.65-2.61 (m, 2H), 2.16-2.09 (m, 2H); 13C NMR (CDCl3) δ 169.8, 158.4 (J=242.9 Hz), 135.7 (J=2.7 Hz), 128.5 (J=7.7 Hz), 115.7 (J=8.1 Hz), 115.1 (J=22.7), 113.8 (J=22.3 Hz), 42.6, 40.3, 31.5, 30.1, 25.5.

Workup

  1. stirringby stirring at rt 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. customThe product was purified by flash CC (SiO2; DCM)

Sources & evidence

ORD record
ord-7ac819867cb34fb3a31c535429c98dd7
Source dataset
uspto-grants-2009_08
Patent number
US07576100B2

Reaction notes

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