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

HRID 574231Notes

Reaction equation

HRID 574231 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>[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

5

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 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

3-(2,5-Dimethyl-pyrrol-1-yl)-6-methoxy-5-trifluoromethyl-pyridine-2-carboxylic acid (833 mg, 2.65 mmol) was dissolved in EtOH (45 ml) and water (23 ml). To this mixture was added TEA (1.102 ml, 7.95 mmol) followed by hydroxylamine hydrochloride (1842 mg, 26.5 mmol). The resulting mixture was heated at reflux overnight. After cooling to RT, the mixture was stirred with 20 g Isolute® PE-AX (silica-based sorbent with a chemically bonded quaternary amine functional group used for isolation of acidic compounds) for 30 mins, washed with MeOH (100 ml), 1M HCl: MeCN 2:8 (200 ml). The organic portion was removed and the mixture was filtered. The filtrate was acidified with 2M HCl (50 ml) and the EtOH was removed in vacuo. The aqueous portion was extracted with DCM (200 ml) and the organic extract was dried (MgSO4) and concentrated in vacuo to give a brown oil. Purification by chromatography on silica eluting with DCM: MeOH afforded the title product as a yellow solid: LC-MS Rt=2.90 min [M+H]+ 237 (Method 10minLC_v002)

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureat reflux overnight
  3. customfor 30 mins
  4. washwashed with MeOH (100 ml), 1M HCl: MeCN 2:8 (200 ml)
  5. customThe organic portion was removed
  6. filtrationthe mixture was filtered
  7. customthe EtOH was removed in vacuo
  8. extractionThe aqueous portion was extracted with DCM (200 ml)
  9. extractionthe organic extract
  10. dry with materialwas dried (MgSO4)
  11. concentrationconcentrated in vacuo
  12. customto give a brown oil
  13. customPurification by chromatography on silica eluting with DCM

Sources & evidence

ORD record
ord-e68596b2f1934a0a948797af79b28179
Source dataset
uspto-grants-2015_05
Patent number
US09034879B2

Reaction notes

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