Hydrochloric Acid → Hydrochloric Acid

HRID 547573Notes

Reaction equation

HRID 547573 reaction equation
[OH:1][C:2]1[CH:7]=[C:6]([S:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16](=[O:26])[C:17]3[CH:22]=[CH:21][C:20]([N+:23]([O-])=O)=[CH:19][CH:18]=3)=[CH:11][CH:10]=2)[CH:5]=[CH:4][N:3]=1.CCO.[ClH:30]>[Fe].O>[ClH:30].[NH2:23][C:20]1[CH:21]=[CH:22][C:17]([C:16]([NH:15][C:12]2[CH:11]=[CH:10][C:9]([S:8][C:6]3[CH:5]=[CH:4][N:3]=[C:2]([OH:1])[CH:7]=3)=[CH:14][CH:13]=2)=[O:26])=[CH:18][CH:19]=1

Participants

7

Reactant 3

HCID 313Hydrochloric Acid2×HCID 702EthanolHCID 178522269HCID 178522269, compound

Product 2

HCID 313Hydrochloric AcidHCID 178507638HCID 178507638, compound

Reagents, catalysts & solvents 2

HCID 23925IronCatalyst2×HCID 962WaterSolvent

Procedure

Nitro compound 14 (0.48 g, 1.18 mmol) was suspended in 2:1 EtOH:H2O (100 mL) and the resulting suspension brought to reflux. To this mixture was sequentially added Fe dust (0.30 g, 9.59 mmol) and c.HCl (2 mL), and the resulting suspension refluxed for 15 min. TLC and LCMS analysis at this time showed that the reaction was incomplete, thus further quantities of Fe dust (0.80 g, 14.29 mmol) and c.HCl (10 mL) were added, and the mixture refluxed for a further 50 min. After this time, the reaction was complete, and thus the reaction mixture was filtered hot through a pad of Celite, and solvent was removed under reduced pressure. The residue was dried via two MeOH-azeotrope cycles, and then re-dissolved in MeOH and stirred overnight with Celite and activated charcoal. The resulting slurry was filtered through a pad of Celite, and solvent was removed under reduced pressure. The residue was re-dissolved in MeOH and adsorbed onto a quantity of silica gel, and the resulting silica adsorbate was purified by column chromatography on silica gel, eluting with 1%→20% MeOH:CH2Cl2 (with 0.5% aq.NH3), to afford crude 15. This material was purified further by re-precipitation from MeOH:methanolic HCl:EtOAc, to afford amine 15 as an amorphous cream solid (15 mg, 3%—presumably much material lost by adsorption to activated charcoal,; latter was extracted several times, to little avail); 1H NMR [(CD3)2SO]: δ 11.40 (v v br s, 1H, quinolinyl-N+—H), 10.08 (s, 1H, ArH), 7.94 (ddd, J=9.40, 4.51, 2.59 Hz, 2H, ArH), 7.78 (d, J=8.67 Hz, 2H, ArH), 7.52 (ddd, J=9.40, 4.49, 2.61 Hz, 2H, ArH), 7.27 (d, J=6.95 Hz, 1H, ArH), 6.71 (d, J=8.52 Hz, 2H, ArH), 5.96 (dd, J=6.96, 1.93 Hz, 1H, ArH) [ArOH & ArNH2 not visible]; LCMS (APCI+): 338 (100%), 423 (60%), 169 (40%).

Workup

  1. temperatureto reflux
  2. temperaturethe mixture refluxed for a further 50 min
  3. filtrationthus the reaction mixture was filtered hot through a pad of Celite, and solvent
  4. customwas removed under reduced pressure
  5. dry with materialThe residue was dried via two MeOH-azeotrope cycles
  6. dissolutionre-dissolved in MeOH
  7. filtrationThe resulting slurry was filtered through a pad of Celite, and solvent
  8. customwas removed under reduced pressure
  9. dissolutionThe residue was re-dissolved in MeOH
  10. customthe resulting silica adsorbate was purified by column chromatography on silica gel
  11. washeluting with 1%→20% MeOH
  12. customCH2Cl2 (with 0.5% aq.NH3), to afford crude 15
  13. customThis material was purified further by re-precipitation from MeOH

Sources & evidence

ORD record
ord-02a74411c4f747b4b25b95880c4c732b
Source dataset
uspto-grants-2011_05
Patent number
US07939546B2

Reaction notes

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