Triethylamine → 3-Amino-5,6-bis-trifluoromethyl-pyridine-2-carboxylic acid (3,3,3-trifluoro-2-hydroxy-2-methyl-propyl)-amide

Temperatur

98 °C

To a stirred solution of 3-(2,5-dimethyl-pyrrol-1-yl)-5,6-bis-trifluoromethyl-pyridine-2-carboxylic acid (3,3,3-trifluoro-2-hydroxy-2-methyl-propyl)-amide (985 mg, 2.064 mmol) in 2:1 EtOH/H2O (7.5 ml) was added hydroxylamine hydrochloride (1.43 g, 20.64 mmol) followed by NEt3 (575 ml, 4.13 mmol). The reaction mixture was heated to reflux (˜98° C.) for 11.5 hours and then allowed to cool to RT. The solvent was removed in vacuo and the resulting residue was partitioned between EtOAc (25 ml) and water (25 ml). The aqueous layer was separated and extracted with EtOAc (2×25 ml) and the combined organic extracts were washed with brine (50 ml), dried (MgSO4) and concentrated in vacuo. The crude material was purified by chromatography on silica eluting with 0-25% EtOAc in iso-hexane to afford the title product as a pale yellow solid; LC-MS: Rt 1.24 min; MS m/z 400.0 [M+H]+; Method 2minLC_v003.

1. temperatureThe reaction mixture was heated
2. temperatureto cool to RT
3. customThe solvent was removed in vacuo
4. customthe resulting residue was partitioned between EtOAc (25 ml) and water (25 ml)
5. customThe aqueous layer was separated
6. extractionextracted with EtOAc (2×25 ml)
7. washthe combined organic extracts were washed with brine (50 ml)
8. dry with materialdried (MgSO4)
9. concentrationconcentrated in vacuo
10. customThe crude material was purified by chromatography on silica eluting with 0-25% EtOAc in iso-hexane

ORD-Eintrag

ord-cbd37fec9e95436abdfebce84928ed2b

Quelldatensatz

uspto-grants-2012_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08247436B2