Water → HCID 73700053, compound

Temperature

0 °C

A solution of 1-(3-cyano)phenyl-2-(trifluoroacetyl)hydrazine (1, 22.9 g, 0.1 mol) in ethyl acetate (180 mL) was treated with p-toluenesulfonyl chloride (24.8 g, 0.13 mol, 1.3 equiv) at 0° C. under N2, and the resulting reaction was added dropwise a solution of N-methylmorpholine (NMM, 11.11 g, 12.1 mL, 0.11 mmol, 1.1 equiv) at 0° C. under N2. The reaction mixture was then stirred at 0° C. for 10 min before being gradually warmed to room temperature for 3-4 h. When the HPLC showed that the reaction had a greater than 95% conversion, the reaction mixture was treated with water (200 mL) and EtOAc (300 mL). The resulting mixture was stirred at room temperature for 30 min. The two layers were then separated, and the aqueous layer was extracted with EtOAc (100 mL). The combined organic extracts were washed with water (2×100 mL) and saturated NaCl aqueous solution (100 mL), dried over MgSO4, and concentrated in vacuo. The residual ethyl acetate solution (100 mL) was added heptanes (400 mL), and the resulting mixture was stirred at room temperature for 1 h to precipitate the desired tosylate. The solids were collected by filtration, washed with EtOAc-hexanes (1:5, 2×50 mL) and dried in vacuo. The crude desired 2,2,2-trifluoro-N-(3-cyanophenyl)ethanehydrazonoyl tosylate (5, 31.03 g, 38.3 g theoretical, 81%) was obtained as pale-yellow solids, which was found to be >96% pure by HPLC. The only observable impurity (3-4%) was found to be the corresponding iminoyl chloride (2), which will not affect the following cycloaddition reaction. The analytically pure product (5) was obtained from flash column chromatography (SiO2, 5-20% EtOAc-hexanes gradient elution) purification or recrystalization (EtOAc/heptanes) of the crude 5 obtained above. For 5: CIMS m/z 382 (M+−H, C16H12F3N3O3S).

1. customthe resulting reaction
2. temperaturebefore being gradually warmed to room temperature for 3-4 h
3. stirringThe resulting mixture was stirred at room temperature for 30 min
4. customThe two layers were then separated
5. extractionthe aqueous layer was extracted with EtOAc (100 mL)
6. washThe combined organic extracts were washed with water (2×100 mL) and saturated NaCl aqueous solution (100 mL)
7. dry with materialdried over MgSO4
8. concentrationconcentrated in vacuo
9. additionThe residual ethyl acetate solution (100 mL) was added heptanes (400 mL)
10. stirringthe resulting mixture was stirred at room temperature for 1 h
11. customto precipitate the desired tosylate
12. filtrationThe solids were collected by filtration
13. washwashed with EtOAc-hexanes (1:5, 2×50 mL)
14. customdried in vacuo
15. customThe crude desired 2,2,2-trifluoro-N-(3-cyanophenyl)ethanehydrazonoyl tosylate (5, 31.03 g, 38.3 g theoretical, 81%) was obtained as pale-yellow solids, which
16. customthe following cycloaddition reaction

ORD record

ord-db085e41df0443819daccdc386ec563d

Source dataset

uspto-grants-2002_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06465656B2