Pyridine → HCID 140597278, compound

Temperature

57 °C

To a solution of ethyl 3-(2,2,2-trifluoroacetyl)benzoate (500 mg, 2.15 mmol) in ethanol was added pyridine (5 mL) and hydroxylamine hydrochloride (500 mg, 7.2 mmol) and the resulting mixture stirred at 57° C. for 3 hours. The reaction mixture was cooled and passed through an ion exchange column eluting with methanol (30 mL). The methanol solution was evaporated in vacuo to give (E)-ethyl 3-(2,2,2-trifluoro-1-(hydroxyimino)ethyl)benzoate as an oil in 71% yield, 401 mg which was used in the next step without further purification. To a stirred solution of (E)-ethyl 3-(2,2,2-trifluoro-1-(hydroxyimino)ethyl)benzoate (401 mg, 1.54 mmol) in dichloromethane (10 mL) was added DMAP (17 mg, 0.14 mmol) and the mixture cooled to 0° C. 4-methylbenzene-1-sulfonyl chloride (331 mg, 1.74 mmol) was added portion-wise as a solution in dichloromethane (5 mL). The reaction mixture was then left to stand at room temperature for 18 hours. The mixture was diluted with water (10 mL) and the organic layer separated, dried over magnesium sulfate and evaporated in vacuo to afford (E)-ethyl 3-(2,2,2-trifluoro-1-((tosyloxy)imino)ethyl)benzoate as an oil in 78% yield, 500 mg. This material was used in the next step without further purification. A mixture of (E)-ethyl 3-(2,2,2-trifluoro-1-((tosyloxy)imino)ethyl)benzoate (500 mg, 1.2 mmol) in diethylether (5 mL) in a 3-necked flask equipped with an internal thermometer and condenser was cooled to −78° C. Ammonia gas was introduced for 5 min and then stirring continued for 45 min. The reaction mixture was warmed to −33° C. and stirred for 2 hours after which it was allowed to warm to room temperature overnight with stirring.

1. temperatureThe reaction mixture was cooled
2. washeluting with methanol (30 mL)
3. customThe methanol solution was evaporated in vacuo

ORD record

ord-11bb20a5d2134eb7b7398dca1219b814

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08846698B2