Hydrochloric Acid → 5-Chloro-3-[(2,6-difluorobenzyl)oxy]pyridine-2-amine

HRID 2401630Notes

Reaction equation

HRID 2401630 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([O:11][CH2:12][C:13]2[C:18]([F:19])=[CH:17][CH:16]=[CH:15][C:14]=2[F:20])[C:5]([N+:8]([O-])=O)=[N:6][CH:7]=1.Cl.C([O-])(=O)C.[Na+]>C(O)C.[Fe]>[Cl:1][C:2]1[CH:3]=[C:4]([O:11][CH2:12][C:13]2[C:14]([F:20])=[CH:15][CH:16]=[CH:17][C:18]=2[F:19])[C:5]([NH2:8])=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 517045Sodium AcetateHCID 867178765-Chloro-3-[(2,6-difluorobenzyl)oxy]-2-nitropyridine

Product 1

HCID 867178775-Chloro-3-[(2,6-difluorobenzyl)oxy]pyridine-2-amine

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 702EthanolSolvent

Procedure

59.7 g of 5-chloro-3-[(2,6-difluorobenzyl)oxy]-2-nitropyridine (Example 13A; 199 mmol, 1 equivalent) were initially charged in 600 ml of ethanol, 34.4 g of iron powder (616 mmol, 3.1 equivalents) were added and the mixture was heated to reflux. 152 ml of concentrated hydrochloric acid were slowly added dropwise and the mixture was boiled at reflux for a further 30 min. The reaction mixture was cooled and stirred into an ice/water mixture. The resulting mixture was adjusted to pH 5 using sodium acetate, the solid obtained was filtered off, washed with water and air-dried and then dried under reduced pressure at 50° C. This gave 52.7 g (98% of theory) of the title compound.

Workup

  1. temperaturethe mixture was heated to reflux
  2. temperatureat reflux for a further 30 min
  3. temperatureThe reaction mixture was cooled
  4. customthe solid obtained
  5. filtrationwas filtered off
  6. washwashed with water
  7. customair-dried
  8. customdried under reduced pressure at 50° C

Sources & evidence

ORD record
ord-7c8c5992aaa64a64af8b1b987d96572d
Source dataset
uspto-grants-2014_08
Patent number
US08796305B2

Reaction notes

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