Methanol → 8-Fluoro-1-(2-(1-methylpyrrolidin-2-yl)ethyl)-6-nitro-1,2,3,4-tetrahydroquinoline

HRID 1922476Notes

Reaction equation

HRID 1922476 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][CH:21]1[CH2:25][CH2:24][CH2:23][N:22]1[CH3:26].CO>CN(C)C=O.O.ClCCl.C(OCC)(=O)C>[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][CH:21]1[CH2:25][CH2:24][CH2:23][N:22]1[CH3:26])[CH2:9][CH2:8][CH2:7]2

Participants

9

Reactant 4

HCID 887MethanolHCID 24758Sodium hydrideHCID 3017050Pyrrolidine, 2-(2-chloroethyl)-1-methyl-, hydrochloride (1:1)HCID 598071108-Fluoro-6-nitro-1,2,3,4-tetrahydroquinoline

Product 1

HCID 598070798-Fluoro-1-(2-(1-methylpyrrolidin-2-yl)ethyl)-6-nitro-1,2,3,4-tetrahydroquinolineYield 85%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

To a stirred solution of 8-fluoro-6-nitro-1,2,3,4-tetrahydroquinoline (500 mg, 2.55 mmol) in N,N-dimethylformamide (11 ml), cooled to 0° C. was added sodium hydride, 60% (326 mg, 8.16 mmol) with vigorous stirring. When the bubbling subsided, 2-(2-chloroethyl)-1-methylpyrrolidine hydrochloride (938 mg, 5.10 mmol) was added and the reaction mixture (dark red) was stirred at 90° C. for 1 h. TLC analysis showed that the reaction mixture was 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 a 1:1 mixture of brine and water (3×), then brine (1×), dried over sodium sulfate, filtered and concentrated. The residue was chromatographed in ethyl acetate, then 10% methanol in 1:1 ethyl acetate:dichloromethane, giving the desired 8-fluoro-1-(2-(1-methylpyrrolidin-2-yl)ethyl)-6-nitro-1,2,3,4-tetrahydroquinoline (665 mg, 2.164 mmol, 85% yield). 1H NMR (DMSO-d6) δ 7.77 (dd, J=15, 2.7 Hz, 1H), 7.71 (d, J=2.4 Hz, 1H), 3.43-3.32 (m, 4H), 2.94-2.88 (m, 1H), 2.78-2.73 (m, 2H), 2.19 (s, 3H), 2.06-1.97 (m, 2H), 1.91-1.83 (m, 4H); 1.64-1.56 (m, 4H).

Workup

  1. temperatureThe mixture was then cooled to room temperature
  2. extractionextracted with ethyl acetate (3×)
  3. washThe combined organics were then washed with a 1:1 mixture of brine and water (3×)
  4. dry with materialbrine (1×), dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was chromatographed in ethyl acetate

Sources & evidence

ORD record
ord-a3bdcbca4ebe49f5b23de4b28edbdcc4
Source dataset
uspto-grants-2012_05
Patent number
US08173813B2

Reaction notes

Loading…