3,3,3-Trifluoro-2-hydroxy-2-methylpropanoic acid → 3-Amino-6-bromo-N'-(3,3,3-trifluoro-2-hydroxy-2-methylpropanoyl)-5-(trifluoromethyl)picolinohydrazide

Temperature

0 °C

A cooled (0° C.) solution of 3-amino-6-bromo-5-(trifluoromethyl)picolinohydrazide (Intermediate H) (15 g, 50.2 mmol) in dry NMP (50 ml) was treated with 3,3,3-trifluoro-2-hydroxy-2-methylpropanoic acid (8.72 g, 55.2 mmol), HATU (20.98 g, 55.2 mmol) followed by dropwise addition of TEA (15.38 ml, 110 mmol) over 10 minutes. The orange solution was stirred at 0° C. and allowed to warm to RT and stirred for 3 days. The reaction mixture was partitioned between EtOAc (200 mL) and 1M NaOH (200 mL), shaken and separated. The organic portion washed with brine (100 mL), dried (MgSO4) and concentrated in vacuo to give an orange oil. The oil was taken up in methanol (50 mL) and triturated with water (300 mL) to afford the title compound as a yellow solid;

1. temperatureto warm to RT
2. stirringstirred for 3 days
3. customThe reaction mixture was partitioned between EtOAc (200 mL) and 1M NaOH (200 mL)
4. stirringshaken
5. customseparated
6. washThe organic portion washed with brine (100 mL)
7. dry with materialdried (MgSO4)
8. concentrationconcentrated in vacuo
9. customto give an orange oil
10. customtriturated with water (300 mL)

ORD record

ord-56477a2ddc4c48b4b2d9dafe154eb50d

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09034879B2