Ammonium Chloride → HCID 86703359, compound

HRID 1050846Notes

Reaction equation

HRID 1050846 reaction equation
[F:1][C:2]1[CH:19]=[C:18]([N+:20]([O-])=O)[C:17]([F:23])=[CH:16][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]([NH:11][C:12](=[O:15])[CH2:13][CH3:14])[CH:6]=1.[NH4+].[Cl-]>CCO.O.[Fe]>[NH2:20][C:18]1[C:17]([F:23])=[CH:16][C:3]([O:4][C:5]2[CH:10]=[CH:9][N:8]=[C:7]([NH:11][C:12](=[O:15])[CH2:13][CH3:14])[CH:6]=2)=[C:2]([F:1])[CH:19]=1

Participants

6

Reactant 2

HCID 25517Ammonium ChlorideHCID 86703360HCID 86703360, compound

Product 1

HCID 86703359HCID 86703359, compoundYield 70.5%

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

To a suspension of N-(4-(2,5-difluoro-4-nitrophenoxy)pyridin-2-yl)propionamide (27.2 g, 84.2 mmol) in EtOH (750 mL) was added a solution of NH4Cl (18 g, 337 mmol) in water (188 mL) and Fe powder (97%, 325 mesh, 18.8 g, 337 mmol) in one portion at RT. The mixture was then heated at 80° C. for 1 h, cooled to ambient temp, filtered through a bed of diatomaceous earth, and washed with MeOH (1 L). The combined filtrates were concentrated to dryness and purified by silica gel chromatography (EtOAc/hexanes) to give N-(4-(4-amino-2,5-difluorophenoxy)pyridin-2-yl)propionamide (17.4 g, 70.5% yield). 1H-NMR (400 MHz, CDCl3): δ 8.07 (d, J=5.6 Hz, 1 H), 8.00 (br s, 1 H), 7.77 (d, J=2 Hz, 1 H), 6.85 (dd, J=10.4, 7.2 Hz, 1 H), 6.63-6.58 (m, 2 H), 3.79 (s, 2 H), 2.38 (q, J=7.6 Hz, 2 H), 1.20 (t, J=7.6 Hz, 3H); MS (ESI): m/z 294.1 (M+H+).

Workup

  1. temperaturecooled to ambient temp
  2. filtrationfiltered through a bed of diatomaceous earth
  3. washwashed with MeOH (1 L)
  4. concentrationThe combined filtrates were concentrated to dryness
  5. custompurified by silica gel chromatography (EtOAc/hexanes)

Sources & evidence

ORD record
ord-534317344bd24be8b965a15176690334
Source dataset
uspto-grants-2016_07
Patent number
US09387202B2

Reaction notes

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