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17th July 2017 @ 19:24
Scheme:  [data]20946[/data] SM/P (Trimethylsilyl)diazomethane methanol, anhydrous 2-(4-chlorophenyl)-3-oxo-3-phenylpropanenitrile (Z)-2-(4-chlorophenyl)-3-methoxy-3-phenylacrylonitrile mw 114.2230 32.04 255.05 269.73 Equiv 1.20   1.00 1.00 mmol 8.33   6.94 6.94 mg     1770 1872 mL 4.16 31.7     g/mL   0.791     M 2.0         in Et2O       bp ˚C   64.7     7/6/17.  To a 1-neck 24/40 x 250 mL RB with stir bar and septum were added 150 mL anhydrous toluene and 32 mL anhydrous methanol with stirring under a balloon of Ar.  To this stirring, clear, colorless solution was added 4.16 mL of a 2.0 M solution of TMS-diazomethane dropwise at about 1 drop/second to give a clear, light yellow/brown solution which was stirred at RT for 5 hours. The Ar balloon was removed, and mineral oil bubbler line was connected via needle through the septum.  A clear, colorless solution of 2-(4-chlorophenyl)-3-oxo-3-phenylpropanenitrile and (Z)-2-(4-chlorophenyl)-3-hydroxy-3-phenylacrylonitrile (both products from step 1) in 8 mL of anhydrous methanol was then added dropwise at about 1 drop/second. N2 gas generation was evident by bubbling of the bubbler.  The resulting clear, colorless solution was allowed to stir at RT for 30 mins. 7/7/17 The reaction mixture was diluted with 15 mL Et2O and 80 mL 10% ac AcOH.  The aqueous phase was extracted 3x Et2O, and the combined organic layer was washed with saturated aqueous K2CO3, dried over MgSO4, and concentrated to give oil (1.01 g, 3.74 mmol, 54% yield). It appeared from the TLC that fractions 63-80 from the previous step reacted, while fractions 14-19 did not. 20:80 EtOAc:Hexanes [data]20950[/data] 7/11/17 The crude product was purified by column chromatography, using 10:90 EtOAc: Hexanes as the starting eluent, and then increasing to 20:80 EtOAc: Hexanes. Fraction 23-35 were collected, and the solvent was removed under reduced pressure to yield an amber/brown-colored oil (0.132 g, 0.489 mmol, 7% yield).  [data]20952[/data] [data]20946[/data]
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