Tetrahydrofuran → 6-Nitro-1-(3-(pyrrolidin-1-yl)propyl)-1,2,3,4-tetrahydroquinoline

HRID 1922525Notes

Reaction equation

HRID 1922525 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[N:10]([CH2:14][CH2:15][CH2:16][N:17]1[CH2:21][CH2:20][CH2:19][CH2:18]1)[C:9](=O)[CH2:8][CH2:7]2)([O-:3])=[O:2].C1COCC1>>[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[N:10]([CH2:14][CH2:15][CH2:16][N:17]1[CH2:21][CH2:20][CH2:19][CH2:18]1)[CH2:9][CH2:8][CH2:7]2)([O-:3])=[O:2]

Participants

3

Reactant 2

HCID 8028TetrahydrofuranHCID 533922596-nitro-1-(3-(pyrrolidin-1-yl)propyl)-3,4-dihydroquinolin-2(1H)-one

Product 1

HCID 533923476-Nitro-1-(3-(pyrrolidin-1-yl)propyl)-1,2,3,4-tetrahydroquinolineYield 56.6%

Conditions

Temperature
0 °C

Procedure

A solution of 6-nitro-1-(3-(pyrrolidin-1-yl)propyl)-3,4-dihydroquinolin-2(1H)-one (500 mg, 1.648 mmol) in borane tetrahydrofuran complex, 1 M in THF (16.500 mL, 16.50 mmol) was stirred overnight at 60° C. The reaction mixture was then cooled to 0° C., and quenched with methanol. The resulting solution was concentrated, and the residue was stirred in refluxing methanol and 1N HCl for 1 h. The mixture was then neutralized with 1N sodium hydroxide, then extracted with dichloromethane (3×). The combined organics were dried, filtered and concentrated then chromatographed on silica gel using ethyl acetate, followed by 5-10% (2M NH3 in MeOH) in dichloromethane as eluent to give the desired 6-nitro-1-(3-(pyrrolidin-1-yl)propyl)-1,2,3,4-tetrahydroquinoline (270 mg, 0.933 mmol, 56.6% yield). 1H NMR (DMSO-d6) δ 7.87 (dd, J=9.3, 2.7 Hz, 1H), 7.77 (d, J=2.7 Hz, 1H), 6.70 (d, J=9.3 Hz, 1H), 3.46-3.38 (m, 4H), 2.74 (t, J=6 Hz, 2H), 2.43-2.38 (m, 6H), 1.86-1.82 (m, 2H), 1.74-1.67 (m, 6H).

Workup

  1. customquenched with methanol
  2. concentrationThe resulting solution was concentrated
  3. temperaturein refluxing methanol and 1N HCl for 1 h
  4. extractionextracted with dichloromethane (3×)
  5. customThe combined organics were dried
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customthen chromatographed on silica gel

Sources & evidence

ORD record
ord-279ed9cbf07e4fd2ad8a06ab75da01c2
Source dataset
uspto-grants-2012_05
Patent number
US08173813B2

Reaction notes

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