Water → HCID 86670718, Verbindung

Temperatur

-78 °C

To a solution of (6-chloro-4-iodo-pyridin-3-yl)-methyl-amine (300 mg, 1.12 mmol, prepared according to WO2006013050) in THF (3 mL) was added dropwise at −78° C. lithium bis(trimethylsilyl)amide (1M solution in THF, 1.17 mL, 1.17 mmol). The reaction mixture was stirred at −78° C. for 30 minutes. Then, 3,5-bis(trifluoromethyl)benzoyl chloride (340 mg, 1.23 mmol, CAS RN 1271-19-8) was added at −78° C. and the reaction was stirred for 30 minutes at this temperature. The reaction mixture was allowed to warm to room temperature, stirred for another 1 hour and then poured on 30 mL H2O and 30 mL EtOAc. The layers were separated and the aqueous layer was extracted a second time with 30 mL EtOAc. The combined organic layers were washed with 30 mL brine, dried over MgSO4, filtered and concentrated under vacuum. The residue was purified by silica gel chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:EtOAc (100:0 to 70:30). Colorless solid (328 mg, 57.7%). MS (TurboSpray): m/z=508.0 [M+H]+.

1. stirringthe reaction was stirred for 30 minutes at this temperature
2. temperatureto warm to room temperature
3. stirringstirred for another 1 hour
4. customThe layers were separated
5. extractionthe aqueous layer was extracted a second time with 30 mL EtOAc
6. washThe combined organic layers were washed with 30 mL brine
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated under vacuum
10. customThe residue was purified by silica gel chromatography
11. washeluting with a gradient of n-heptane:EtOAc (100:0 to 70:30)

ORD-Eintrag

ord-c80f5d7a66c946ecba09848c76ca10a0

Quelldatensatz

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08987307B2