Hydrochloric Acid → 3-Fluoro-4-(7-methoxyquinolin-4-yloxy)benzenamine

HRID 2273987Notes

Reaction equation

HRID 2273987 reaction equation
[F:1][C:2]1[CH:20]=[C:19]([N+:21]([O-])=O)[CH:18]=[CH:17][C:3]=1[O:4][C:5]1[C:14]2[C:9](=[CH:10][C:11]([O:15][CH3:16])=[CH:12][CH:13]=2)[N:8]=[CH:7][CH:6]=1.Cl>C1COCC1.CO.[Fe]>[F:1][C:2]1[CH:20]=[C:19]([NH2:21])[CH:18]=[CH:17][C:3]=1[O:4][C:5]1[C:14]2[C:9](=[CH:10][C:11]([O:15][CH3:16])=[CH:12][CH:13]=2)[N:8]=[CH:7][CH:6]=1

Participants

6

Reactant 2

HCID 313Hydrochloric AcidHCID 58533481HCID 58533481, compound

Product 1

HCID 595983543-Fluoro-4-(7-methoxyquinolin-4-yloxy)benzenamine

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 887MethanolSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To 4-(2-fluoro-4-nitrophenoxy)-7-methoxyquinoline (0.900 g, 2.9 mmol) in THF was added methanol (53 ml, 1297 mmol) and 1N HCl (8.6 ml, 8.6 mmol). The resulting mixture was cooled to 0° C. Iron (2.2 g, 40 mmol) was added, and the reaction was allowed to stir at RT for 3.5 hours. The reaction mixture was then diluted with MeOH, filtered through a pad of Celite, and concentrated in vacuo. The residue was then diluted with sat. NaHCO3 (aq) and CH2Cl2. The aqueous layer was separated and extracted three times with CH2Cl2. The combined organic extracts were dried over sodium sulfate and filtered through a pad of silica gel using 10% MeOH/CH2Cl2. The collected fractions were concentrated in vacuo and purified by silica gel chromatography (80 g column; 2% MeOH/CH2Cl2 for 10 minutes then 3.5% MeOH/CH2Cl2 for 10 minutes). Fractions containing pure product were concentrated to yield 3-fluoro-4-(7-methoxyquinolin-4-yloxy)benzenamine as a tan solid. Calcd for C16H13FN2O2: [M]+=284. Found: [M+H]+=285.

Workup

  1. filtrationfiltered through a pad of Celite
  2. concentrationconcentrated in vacuo
  3. additionThe residue was then diluted with sat. NaHCO3 (aq) and CH2Cl2
  4. customThe aqueous layer was separated
  5. extractionextracted three times with CH2Cl2
  6. dry with materialThe combined organic extracts were dried over sodium sulfate
  7. filtrationfiltered through a pad of silica gel using 10% MeOH/CH2Cl2
  8. concentrationThe collected fractions were concentrated in vacuo
  9. custompurified by silica gel chromatography (80 g column
  10. wait2% MeOH/CH2Cl2 for 10 minutes
  11. wait3.5% MeOH/CH2Cl2 for 10 minutes)
  12. additionFractions containing pure product
  13. concentrationwere concentrated

Sources & evidence

ORD record
ord-8908f0b626954c09bf5cabbb73d7d558
Source dataset
uspto-grants-2015_09
Patent number
US09126935B2

Reaction notes

Loading…