Hydroxyamine hydrochloride → 3-Amino-6-methoxy-5-trifluoromethyl-pyridine-2-carboxylic acid

HRID 444927Notes

Reaction equation

HRID 444927 reaction equation
CC1[N:3]([C:8]2[C:9]([C:20]([OH:22])=[O:21])=[N:10][C:11]([O:18][CH3:19])=[C:12]([C:14]([F:17])([F:16])[F:15])[CH:13]=2)C(C)=CC=1.Cl.NO>CCO.O.CCOC(C)=O>[NH2:3][C:8]1[C:9]([C:20]([OH:22])=[O:21])=[N:10][C:11]([O:18][CH3:19])=[C:12]([C:14]([F:15])([F:16])[F:17])[CH:13]=1

Participants

6

Reactant 2

HCID 443297Hydroxyamine hydrochlorideHCID 584423133-(2,5-Dimethyl-pyrrol-1-yl)-6-methoxy-5-trifluoromethyl-pyridine-2-carboxylic acid

Product 1

HCID 584423203-Amino-6-methoxy-5-trifluoromethyl-pyridine-2-carboxylic acid

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-(2,5-Dimethyl-pyrrol-1-yl)-6-methoxy-5-trifluoromethyl-pyridine-2-carboxylic acid (2.1 g, 6.68 mmol) was dissolved in EtOH (40 ml) and water (20 ml). To this mixture was added TEA (2.79 ml, 20.05 mmol) followed by hydroxylamine hydrochloride (4.64 g, 66.8 mmol). The resulting mixture was heated at reflux for 5 hours. After cooling to RT, the mixture was diluted with EtOAc (100 ml) and washed with aqueous HCl (1M, 100 ml). The aqueous phase was back extracted with EtOAc (100 ml) and the combined organic phases washed with brine (100 ml), dried (MgSO4) and concentrated in vacuo to afford the product as an orange solid. The material can be used crude or recrystallised from isohexane-EtOAc (10:1) LC-MS Rt=1.0 min [M+H]+ 237 (Method 2 minLC_v003)

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureat reflux for 5 hours
  3. washwashed with aqueous HCl (1M, 100 ml)
  4. extractionThe aqueous phase was back extracted with EtOAc (100 ml)
  5. washthe combined organic phases washed with brine (100 ml)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8499f83a29414c53846df7ab1c2f5417
Source dataset
uspto-grants-2013_07
Patent number
US08476269B2

Reaction notes

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