Dichloromethane → 2-(8-Fluoro-6-nitro-3,4-dihydroquinolin-1(2H)-yl)-N,N-dimethylethanamine

HRID 1922462Notes

Reaction equation

HRID 1922462 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N+:12]([O-:14])=[O:13])[CH:5]=[C:6]2[C:11]=1[NH:10][CH2:9][CH2:8][CH2:7]2.[H-].[Na+].Cl.Cl[CH2:19][CH2:20][N:21]([CH3:23])[CH3:22].ClCCl>CN(C)C=O.O>[F:1][C:2]1[CH:3]=[C:4]([N+:12]([O-:14])=[O:13])[CH:5]=[C:6]2[C:11]=1[N:10]([CH2:19][CH2:20][N:21]([CH3:23])[CH3:22])[CH2:9][CH2:8][CH2:7]2

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 24758Sodium hydrideHCID 11636816N,N-Dimethylaminoethyl chloride hydrochlorideHCID 598071108-Fluoro-6-nitro-1,2,3,4-tetrahydroquinoline

Product 1

HCID 533922632-(8-Fluoro-6-nitro-3,4-dihydroquinolin-1(2H)-yl)-N,N-dimethylethanamineYield 56.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 8-fluoro-6-nitro-1,2,3,4-tetrahydroquinoline (670 mg, 3.42 mmol) in N,N-Dimethylformamide (15 ml), cooled to 0° C. was added sodium hydride, 60% (437 mg, 10.93 mmol) with vigorous stirring. When bubbling subsided, 2-chloro-N,N-dimethylethanamine hydrochloride (984 mg, 6.83 mmol) was added and the reaction mixture (dark red) was stirred at room temperature. After 2 h, no product was observed so the reaction was heated to 90° C. and stirred. After 1 h, TLC showed the reaction to be complete. The mixture was then cooled to room temperature, diluted with water and extracted with ethyl acetate (3×). The combined organics were then washed with 1:1 water:brine (2×), then brine (1×). The organic phase was dried, filtered and concentrated, then chromatographed in 0-10% (2M NH3 in methanol) in 1:1 ethyl acetate:dichloromethane, giving the desired 2-(8-fluoro-6-nitro-3,4-dihydroquinolin-1(2H)-yl)-N,N-dimethylethanamine (514 mg, 1.923 mmol, 56.3% yield). NMR (DMSO-d6) δ 7.77 (dd, J=15 Hz, 2.7 Hz, 1H); 7.72 (m, 1H); 3.55-3.48 (m, 2H); 3.43-3.39 (m, 2H); 2.78-2.74 (m, 2H), 2.49-2.44 (m, 2H); 2.16 (s, 6H); 1.88-1.79 (m, 2H). ESI-MS (m/z, %): 268 (MH+, 100); 223 (5).

Workup

  1. customWhen bubbling
  2. temperaturewas heated to 90° C.
  3. stirringstirred
  4. waitAfter 1 h
  5. customthe reaction
  6. temperatureThe mixture was then cooled to room temperature
  7. extractionextracted with ethyl acetate (3×)
  8. washThe combined organics were then washed with 1:1 water
  9. customThe organic phase was dried
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customchromatographed in 0-10% (2M NH3 in methanol) in 1:1 ethyl acetate

Sources & evidence

ORD record
ord-69daaff142b84c16900e9c1714a0db45
Source dataset
uspto-grants-2012_05
Patent number
US08173813B2

Reaction notes

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