Ammonium Hydroxide → HCID 3054979, compound

A suspension of 25 g of the product of Step A in about 10 volumes of water cooled in an ice bath was made basic by addition of ammonium hydroxide and the mixture was extracted with ethyl acetate. The organic extract was washed with water, dried over magnesium sulfate and evaporated to dryness under reduced pressure to obtain 22 g of 3-(4-chloro-3-trifluoromethyl-phenyl)-1-benzyl-1,2,5,6-tetrahydropyridine which were dissolved in 250 ml of anhydrous xylene. The solution was refluxed for 5 hours with vigorous stirring while adding 10 g of phosphoric acid anhydride each hour for a total of 50 g and the mixture was allowed to stand overnight at room temperature. Then, ice was continuously added to the reaction mixture and the mass formed was dissolved in a mixture of water, ethyl acetate and triethylamine. After total dissolution, it was ascertained that the mixture was basic and the organic phase was washed with aqueous sodium chloride solution. The wash water was extracted with ethyl acetate and the combined organic phases were dried over magnesium sulfate and evaporated to dryness under reduced pressure. The residue was chromatographed over silica gel and was eluted with a 9-1 cyclohexane-ethyl acetate mixture. The fractions corresponding to the desired product were distilled to dryness and the residue was taken up in methylene chloride. The solution was filtered and the filtrate was evaporated to dryness under reduced pressure to obtain 17 g of the said base. 7 g of the base were dissolved in 50 ml of ethyl acetate and a solution of gaseous hydrogen chloride in ethyl acetate was added thereto dropwise until the pH was acidic. The mixture was iced for 2 hours and was vacuum filtered and the recovered product was washed with ethyl acetate and was dried under reduced pressure to obtain 6.37 g of the desired hydrochloride which was crystallized from isopropanol to obtain 5.25 g of the product melting at 200° C.

1. temperaturecooled in an ice bath
2. extractionthe mixture was extracted with ethyl acetate
3. extractionThe organic extract
4. washwas washed with water
5. dry with materialdried over magnesium sulfate
6. customevaporated to dryness under reduced pressure

ORD record

ord-5db3f815dbc3482eb7f430340fe2e2fb

Source dataset

uspto-grants-1980_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04213989