Iodine → HCID 58257834, compound

To a mixture of butyllithium (2.5 M in hexanes) (6.31 ml, 15.79 mmol) in tetrahydrofuran (125 ml) at 0° C., was added 2,2,6,6-tetramethylpiperidine (3.808 ml, 22.56 mmol). The reaction mixture was then stirred at room temperature for 1 h. The mixture was cooled to −78° C. and then a solution of 4-(6-trifluoromethyl-pyridazin-3-yl)-piperazine-1-carboxylic acid tert-butyl ester (D9) (2.5 g, 7.52 mmol) in tetrahydrofuran (20 ml) was added. The mixture was stirred for 1 h. at −78° C. before adding a solution of iodine (2.29 g, 9.024 mmol) in tetrahydrofuran (10 ml). The mixture was stirred at −78° C. for 1 h. and then diluted with a 10% solution of acetic acid in tetrahydrofuran. The mixture was then allowed to reach room temperature and then the solvent was evaporated in vacuo. The residue was diluted with dichloromethane and extracted with water. The organic layer was separated, dried (MgSO4), filtered and the solvent evaporated in vacuo. The residue was precipitated from diethyl ether to yield D10 (2.81 g, 82%) as a light yellow solid. C14H18F31N4O2 requires 458; Found 459 (MH+).

1. temperatureThe mixture was cooled to −78° C.
2. stirringThe mixture was stirred for 1 h. at −78° C.
3. stirringThe mixture was stirred at −78° C. for 1 h.
4. customto reach room temperature
5. customthe solvent was evaporated in vacuo
6. additionThe residue was diluted with dichloromethane
7. extractionextracted with water
8. customThe organic layer was separated
9. dry with materialdried (MgSO4)
10. filtrationfiltered
11. customthe solvent evaporated in vacuo
12. customThe residue was precipitated from diethyl ether

ORD record

ord-b9712f2ca6684eb2ad6a3c48d51db5b7

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08791120B2