Hydrochloric Acid → 3-Bromo-7-[(R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]furo[3,2-c]pyridin-6-ylamine

HRID 911952Notes

Reaction equation

HRID 911952 reaction equation
[Br:1][C:2]1[C:6]2[CH:7]=[N:8][C:9]([N+:23]([O-])=O)=[C:10]([O:11][C@@H:12]([C:14]3[C:19]([Cl:20])=[CH:18][CH:17]=[C:16]([F:21])[C:15]=3[Cl:22])[CH3:13])[C:5]=2[O:4][CH:3]=1.Cl>CCO.CCOC(C)=O.[Fe]>[Br:1][C:2]1[C:6]2[CH:7]=[N:8][C:9]([NH2:23])=[C:10]([O:11][C@@H:12]([C:14]3[C:19]([Cl:20])=[CH:18][CH:17]=[C:16]([F:21])[C:15]=3[Cl:22])[CH3:13])[C:5]=2[O:4][CH:3]=1

Participants

6

Reactant 2

HCID 313Hydrochloric Acid2×HCID 578122903-bromo-7-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-6-nitrofuro[3,2-c]pyridine

Product 1

HCID 578127253-Bromo-7-[(R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]furo[3,2-c]pyridin-6-ylamineYield 100%

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-bromo-7-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-6-nitrofuro[3,2-c]pyridine (1.00 g, 2.22 mmol) in EtOH (10 mL) was added iron (0.62 g, 11.1 mmol), followed by 0.1 N aq. HCl (1.1 mL, 0.11 mmol) at 95° C. (bath temp). The resulting mixture was stirred at this temperature for 30 min. Additional 0.1 N aq. HCl (1.1 mL, 0.11 mmol) was added and the mixture was refluxed for another 30 min. TLC and LC-MS showed the reaction was complete. The mixture was diluted with EtOAc (100 mL) and the solid was filtered off through a pad of Celite. The mother liquor was washed with brine (3×25 mL) and dried over anhydrous sodium sulfate. Evaporation of solvents under reduced pressure afforded the title compound as a light-yellow semi-solid (930 mg, 100% yield). 1H NMR (CDCl3, 400 MHz): δ=1.87 (d, J=6.6 Hz, 3H), 5.15 (br s, 2H), 6.55 (q, J=6.6 Hz, 1H), 7.06 (dd, J=9.1, 8.1 Hz, 1H), 7.27 (dd, J=9.1, 5.1 Hz, 1H), 7.44 (s, 1H), 7.96 (s, 1H). MS (ES+): 418.91/420.86/422.89 [MH+].

Workup

  1. temperaturethe mixture was refluxed for another 30 min
  2. filtrationthe solid was filtered off through a pad of Celite
  3. washThe mother liquor was washed with brine (3×25 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. customEvaporation of solvents under reduced pressure

Sources & evidence

ORD record
ord-4ebb2526d86d4a02998d8bbc8343146b
Source dataset
uspto-grants-2011_09
Patent number
US08022206B2

Reaction notes

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