Hydrochloric Acid → 5-(1-(trifluoromethyl)cyclobutyl)-2,4-dihydro-3H-1,2,4-triazol-3-one

To a 0° C. solution of 1-trifluoromethyl-1-cyclobutylcarboxylic acid (1.50 g, 8.92 mmol) in DCM (15 mL) was added oxalyl chloride (1.50 g, 11.82 mmol) followed by catalytic amount of DMF. The reaction mixture was stirred at RT for 1 h. The solvent from the reaction mixture was completely evaporated. In a different flask, a suspension of semicarbazide hydrochloride (1.50 g, 13.45 mmol) in water (15 mL) was treated with NaHCO3 (1.50 g, 17.86 mmol) and stirred at RT for 30 minutes till a clear solution forms. To this solution was added the above acid chloride dissolved in EtOAc (20 mL) and the resultant mixture was stirred at RT over night. The organic layer was separated and the aqueous layer was extracted with DCM (2×10 mL). The combined organics were concentrated and the residue was treated with sodium hydroxide (1.50 g, 37.5 mmol) in water (15 mL), heated at 100° C. for 3 h, and stirred for 20 h at RT. The reaction mixture was acidified with conc. HCl to pH 1 and stirred at RT for 1 h. The reaction mixture was concentrated to a small volume under high vacuum and diluted with MeOH. The separated solids were filtered and washed with methanol. The filtrate was evaporated and further dried by azeotropic distillation from toluene to provide 5-(1-(trifluoromethyl)cyclobutyl)-2,4-dihydro-3H-1,2,4-triazol-3-one (1.05 g, 57%) as a light brownish residue, suitable for use without further purification. MS (ESI) m/z: 208.1 (M+H+).

1. customThe solvent from the reaction mixture was completely evaporated
2. stirringstirred at RT for 30 minutes till a clear solution forms
3. customThe organic layer was separated
4. extractionthe aqueous layer was extracted with DCM (2×10 mL)
5. concentrationThe combined organics were concentrated
6. temperatureheated at 100° C. for 3 h
7. stirringstirred for 20 h at RT
8. stirringstirred at RT for 1 h
9. concentrationThe reaction mixture was concentrated to a small volume under high vacuum
10. additiondiluted with MeOH
11. filtrationThe separated solids were filtered
12. washwashed with methanol
13. customThe filtrate was evaporated
14. dry with materialfurther dried by azeotropic distillation from toluene

ORD-Eintrag

ord-90e73cc67b9942cba068a4fb92752a5a

Quelldatensatz

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09193719B2