Ammonium Chloride → 4-(4-Amino-2-fluorophenoxy)-2-[(pyrrolidin-1-yl)carbonylamino]pyridine

HRID 492665Notes

Reaction equation

HRID 492665 reaction equation
[F:1][C:2]1[CH:22]=[C:21]([N+:23]([O-])=O)[CH:20]=[CH:19][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]([NH:11][C:12]([N:14]2[CH2:18][CH2:17][CH2:16][CH2:15]2)=[O:13])[CH:6]=1.[Cl-].[NH4+].C(OCC)(=O)C.O1CCCC1.C(OCC)(=O)C.CCCCCC>C(O)C.O.[Fe]>[NH2:23][C:21]1[CH:20]=[CH:19][C:3]([O:4][C:5]2[CH:10]=[CH:9][N:8]=[C:7]([NH:11][C:12]([N:14]3[CH2:15][CH2:16][CH2:17][CH2:18]3)=[O:13])[CH:6]=2)=[C:2]([F:1])[CH:22]=1

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 21226206Ethyl acetate hexaneHCID 21939870Tetrahydrofuran ethyl acetateHCID 231530114-(2-Fluoro-4-nitrophenoxy)-2-[(pyrrolidin-1-yl)carbonylamino]pyridine

Product 1

HCID 231530584-(4-Amino-2-fluorophenoxy)-2-[(pyrrolidin-1-yl)carbonylamino]pyridineYield 89%

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Procedure

To 4-(2-fluoro-4-nitrophenoxy)-2-[(pyrrolidin-1-yl)carbonylamino]pyridine (2.927 g) dissolved in ethanol (100 ml)-water (20 ml) were added electrolytic iron powder (3.0 g) and ammonium chloride (6.0 g), followed by heating under reflux for 1 hr. The reaction mixture was cooled down to room temperature, and then ethyl acetate-tetrahydrofuran (1:1) was added thereto, followed by stirring. An insoluble portion was filtered through celite, and washed with ethyl acetate and water. The organic layer of the filtrate was separated, washed with water and brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated under a reduced pressure to give a residue, to which ethyl acetate-hexane was added to suspend. Crystals was filtered off and dried under aeration to provide the titled compound (2.378 g, 89%) as pale brown crystals.

Workup

  1. temperatureby heating
  2. temperatureunder reflux for 1 hr
  3. filtrationAn insoluble portion was filtered through celite
  4. washwashed with ethyl acetate and water
  5. customThe organic layer of the filtrate was separated
  6. washwashed with water and brine in this order
  7. dry with materialdried over anhydrous sodium sulfate
  8. customThe solvent was evaporated under a reduced pressure
  9. customto give a residue
  10. filtrationCrystals was filtered off
  11. customdried under aeration

Sources & evidence

ORD record
ord-18f6e2dacde44a8197d92992727a94c3
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

Loading…