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 2 minLC_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-a64d49ff0395451fb01fbf6f68cc181b

Quelldatensatz

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08476269B2