dimethyl 3-(3-chlorophenyl)pentanedioate

反応条件: temp:82.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3-Chlorobenzaldehyde (5 mL, 44.1 mmol), methyl 3-oxobutanoate (9.53 mL, 88 mmol), piperidine (0.654 mL, 6.62 mmol) in MeOH (14.71 mL) were stirred at rt. Over time, the yellow solution turned cloudy, and finally too thick to stir. The solid-like reaction mixture was kept at rt overnight. MeOH (20 mL) was then added, and the yellow solid was broken apart using a spatula, chilled in an ice-water bath and filtered. The solid was washed with cold MeOH (2×10 mL) and then air-dried. A yellowish solid was obtained and the solid was suspended in MeOH (10 mL), then NaOMe (41 mL, 179 mmol, 25% wt in MeOH), followed by water (3.4 mL, 189 mmol) were added. The reaction was warmed to reflux (80-85° C.). During the course of reaction, the suspension became very hard to stir, and additional MeOH (40 mL) was added. After 7 h, the reaction was cooled to rt, and left at rt for 2 days. Water was added to the solid-like reaction mixture to give a brown solution. The reaction mixture was concentrated to remove MeOH, and the residue extracted with EtOAc. The aqueous layer was acidified with concentrated HCl to pH<3, then extracted with EtOAc (3×). The combined organic layers were dried over Na2SO4, filtered and concentrated. The orange oil obtained was dissolved in MeOH (50 mL), then concentrated HCl (0.63 mL) was added, and the mixture was heated at reflux (80° C. in an oil bath). After 6 h, the reaction was cooled to rt and then the reaction was concentrated to remove ⅔ of the MeOH. Water was then added, and a brown oil separated out. The solution was concentrated to remove all organics. The brown oil at the bottom solidified overnight. The solid was filtered, washed with water, air-dried and then dried in a vacuum oven (50° C.) for 2 h, to give a brown solid. The crude solid was purified by silica gel chromatography to give the desired product as a yellow oil (6.23 g, 52%). MS (ESI) m/z: 292.9 (M+Na)+. The solid-like reaction mixture chilled in an ice-water bath filtered The solid was washed with cold MeOH (2×10 mL) air-dried A yellowish solid was obtained were added The reaction was warmed During the course of reaction to stir After 7 h the reaction was cooled to rt left at rt for 2 days to give a brown solution The reaction mixture was concentrated to remove MeOH the residue extracted with EtOAc extracted with EtOAc (3×) The combined organic layers were dried over Na2SO4 filtered concentrated The orange oil obtained the mixture was heated at reflux (80° C. in an oil bath) After 6 h the reaction was cooled to rt the reaction was concentrated to remove ⅔ of the MeOH Water was then added a brown oil separated out The solution was concentrated to remove all organics at the bottom solidified overnight The solid was filtered washed with water air-dried dried in a vacuum oven (50° C.) for 2 h to give a brown solid The crude solid was purified by silica gel chromatography