Stannous chloride dihydrate → 3-Fluoro-5-aminoquinoline

HRID 1519818Notes

Reaction equation

HRID 1519818 reaction equation
[F:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[CH:7][C:6]=2[N+:12]([O-])=O.[F:15][C:16]1[CH:17]=[N:18][C:19]2[C:24]([CH:25]=1)=[C:23]([N+:26]([O-])=O)[CH:22]=[CH:21][CH:20]=2.O.O.[Sn](Cl)Cl>C(OCC)(=O)C.[OH-].[Na+]>[F:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[CH:7][C:6]=2[NH2:12].[F:15][C:16]1[CH:17]=[N:18][C:19]2[CH:20]=[CH:21][CH:22]=[C:23]([NH2:26])[C:24]=2[CH:25]=1

Participants

7

Reactant 3

HCID 61436Stannous chloride dihydrateHCID 154097Quinoline, 3-fluoro-5-nitro-HCID 154250Quinoline, 3-fluoro-8-nitro-

Product 2

HCID 1546773-Fluoro-5-aminoquinolineYield 37%HCID 210733063-Fluoroquinolin-8-amineYield 11%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolvent2×HCID 14798Sodium HydroxideSolvent

Procedure

3-Fluoro-8-nitroquinoline, 3-fluoro-5-nitroquinoline, and tin(II)chloride-dihydrate (68.23 g, 302 mmol) in ethyl acetate (200 ml) was placed into a preheated oil bath at 60° C. After heating for 4 h, the solution was cooled to ambient temperature, diluted with 3 N aq. NaOH, and filtered through a pad of celite. The filtrate was extracted with ethyl acetate, the combined organic extracts were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was flash chromatographed with 19:1, 9:1, 17:3, 4:1, 3:1, 7:3, and 3:2 hexane:ethyl acetate as the eluant to afford 2.14 g (11% yield over two steps) 3-fluoroquinolin-8-amine and 7.02 g (37% yield over two steps) of 3-fluoroquinolin-5-amine. Method [6] retention time 1.57 and 4.02 min by HPLC (M+ 163) and (M+ 163).

Workup

  1. temperatureAfter heating for 4 h
  2. filtrationfiltered through a pad of celite
  3. extractionThe filtrate was extracted with ethyl acetate
  4. dry with materialthe combined organic extracts were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customchromatographed with 19:1, 9:1, 17:3, 4:1, 3:1, 7:3, and 3:2 hexane

Sources & evidence

ORD record
ord-23e033a12435420581526ae9e07dbbad
Source dataset
uspto-grants-2015_07
Patent number
US09073891B2

Reaction notes

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