反应详情

温度

-78 °C

The phenolic ester of 4-({1-[bis(4-chloro-phenyl)methyl]-3-hydroxyazetidin-3-yl}methyl-sulfonylmethyl)-3,6-dihydro-2H-pyridine-1-carbothioic acid is prepared in the following manner: 0.52 g of potassium tert-butoxide is added to a mixture of 0.72 g of the phenolic ester of 4-methylsulfonylmethyl-3,6-dihydro-2H-pyridine-1-carbothioic acid and 0.708 g of 1-[bis(4-chlorophenyl)methyl]azetidin-3-one in 15 cm3 of dry tetrahydrofuran cooled under an inert atmosphere to −78° C. The reaction mixture is stirred at −78° C. for 4 hours and then 0.354 g of 1-[bis(4-chlorophenyl)-methyl]azetidin-3-one are added. After two hours at −78° C., the temperature is allowed to return to 20° C. The reaction mixture is diluted in 100 cm3 of water and then the tetrahydrofuran is evaporated off under 2.7 kPa at 40° C. The aqueous phase is extracted with twice 100 cm3 of ethyl acetate. The organic extracts are combined and dried over magnesium sulfate, concentrated under 2.7 kPa at 40° C. The residue obtained is chromatographed on silica (200 g of silica, Amicon, 20-45 μm, porosity 60 Angstroem, column 5 cm in diameter), eluting with a cyclohexane:ethyl acetate (6:4 by volume) mixture. The fractions with an Rf=11/64 (cyclohexane:ethyl acetate 6:4, silica plate, Merck reference 1.05719, Merck KGaA, 64721 Darmstatd, Germany) are combined and concentrated under 2.7 kPa at 40° C. to give 240 mg of the phenolic ester of 4-({1-[bis(4-chlorophenyl)methyl]-3-hydroxyazetidin-3-yl}methylsulfonylmethyl)-3,6-dihydro-2H-pyridine-1-carbothioic acid.

1. waitAfter two hours at −78° C.
2. customto return to 20° C
3. customthe tetrahydrofuran is evaporated off under 2.7 kPa at 40° C
4. extractionThe aqueous phase is extracted with twice 100 cm3 of ethyl acetate
5. dry with materialdried over magnesium sulfate
6. concentrationconcentrated under 2.7 kPa at 40° C
7. customThe residue obtained
8. customis chromatographed on silica (200 g of silica, Amicon, 20-45 μm, porosity 60 Angstroem, column 5 cm in diameter)
9. washeluting with a cyclohexane:ethyl acetate (6:4 by volume) mixture
10. concentrationconcentrated under 2.7 kPa at 40° C.