3-acetyloxolan-2-one

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: To a solution consisting of 3-acetyldihydro-2(3H)-furanone (25.6 g, 0.2 mole), tryptophol (32.2 g, 0.2 mole) and benzene (700 ml), p-toluenesulfonic acid (0.50 g) is added. The flask is equipped with a water separator and a condenser. The mixture is stirred at reflux for one hr. More p-toluenesulfonic acid (0.50 g) is added and the solution is refluxed for 18 hr. The dark solution is cooled and stirred in presence of silica gel (100 g) for 5 min. The mixture is filtered on diatomaceous earth and charcoal. The silica gel is washed with diethyl ether (2×100 ml) and the filtrates are evaporated to afford an oil which is a mixture of two diasteroisomers of the title compound. If desired, the latter oil can be crystallizated from methanol to obtain crystals (17 g) of isomer A of the title compound, mp 162°-164° C. The mother liquor of this crystallization is evaporated to obtain a residue (20 g) containing mainly isomer B of the title compound. is added at reflux for one hr the solution is refluxed for 18 hr The dark solution is cooled stirred in presence of silica gel (100 g) for 5 min The mixture is filtered on diatomaceous earth and charcoal The silica gel is washed with diethyl ether (2×100 ml) the filtrates are evaporated to afford an oil which

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

実験手順: 2-Acetylbutyrolactone (108 μL, 1 mmol), gabapentin (171 mg, 1 mmol), and piperidine (99 μL, 1 mmol) were mixed in anhydrous methanol (10 mL). After heating under reflux for 6 h, the solvent was removed under reduced pressure to afford the title compound with purity greater than 90%. 1H NMR (CDCl3, 400 MHz): δ 1.34-1.62 (m, 12H), 1.71 (m, 4H), 1.94 (s, 3H), 2.24 (s, 2H), 2.81 (t, J=7.6 Hz, 2H), 2.99 (m, 4H), 3.31 (d, J=6.4 Hz, 2H), 4.23 (t, J=7.6 Hz, 2H), 5.17 (s, br, 2H), 8.64 (t, J=6.4 Hz, 1H). MS (ESI) m/z 280.34 (M−H−). After heating under reflux for 6 h the solvent was removed under reduced pressure

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

実験手順: The fluorination of 2-Acetyl butyrolactone (3.2 gm, 0.025 m) was carried out in a manner similar to that described in Example 6. Work up gave 2-fluoro-2-acetyl butyrolactone(nc) [NMR (CDCl3); 1H, δH =4.5 ppm (m), 2H; 2.87 ppm (m), 1H; 2.55 ppm (m)1H; 2.47 ppm (d), JHF =5.0 Hz, 3H; 19F, δF =-163.4 ppm (ddqd), J=11.8, 11.8, 4.9, and 1.5 Hz]. Accurate mass measurement:--Found (CI, methane), 147.0442; C6H8O3F requires 147.0457]. A small multiplet at -173.8 ppm and triplet of doublets at -237.9 ppm (Jtriplet =46.3 Hz, Jdoublet =6.8 Hz) in the reaction product were attributed to 2-fluoro-2-(fluoroacetyl)butyrolactone. The conversion was ca. 70% and the yield was ca. 85%.

反応条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 75 parts of 2-benzothiazolamine, 76 parts of 3-acetyl-4,5-dihydro-2(3H)-furanone, 2,4 parts of a hydrochloric acid solution 12N and 270 parts of methylbenzene was stirred and refluxed for 2 hours using a water-separator. The reaction mixture was cooled and 323 parts of phosphoryl chloride were added at a temperature between 20° and 25° C. The whole was slowly heated to 110° C. and stirring was continued for 2 hours at this temperature. The solvent was evaporated and the residue was poured onto a mixture of crushed ice and ammonium hydroxide. The product was extracted with trichloromethane. The extract was dried, filtered and evaporated. The residue was purified by columnchromatography over silica gel using a mixture of trichloromethane and methanol (92:8 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from a mixture of 2-propanol and 2,2'-oxybispropane, yielding 39 parts of 3-(2-chloroethyl)-2-methyl-4H-pyrido[2,1-b]benzothiazol-4-one; mp. 144° C. (intermediate 4). refluxed for 2 hours The reaction mixture was cooled stirring The solvent was evaporated the residue was poured onto a mixture of crushed ice and ammonium hydroxide The product was extracted with trichloromethane The extract was dried filtered evaporated The residue was purified by columnchromatography over silica gel using a mixture of trichloromethane and methanol (92:8 by volume) as eluent The pure fractions were collected the eluent was evaporated The residue was crystallized from a mixture of 2-propanol and 2,2'-oxybispropane

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

実験手順: A mixture of 40 parts of 4-methyl-2-thiazolamine, 30 parts of 3-acetyl-4,5-dihydro-2(3H)-furanone and 225 parts of methylbenzene was stirred and refluxed for 2.50 hours with 0.6 parts of hydrochloric acid. After cooling to room temperature, 170 parts of phosphoryl chloride were added. The whole was heated slowly to about 110° C. and stirring was continued for 2 hours at this temperature. The reaction mixture was evaporated and the residue was poured onto crushed ice. Ammonium hydroxide was added till a pH of 8 was reached. The product was extracted with trichloromethane. The extract was dried, filtered and evaporated. The residue was purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (95:5 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from a mixture of 2,2'-oxybispropane and 2-propanol, yielding 19.3 parts of 6-(2-chloroethyl)-3,7-dimethyl-5H-thiazolo[3,2-a]pyrimidin-5 -one (intermediate 1). The whole was heated slowly to about 110° C. stirring The reaction mixture was evaporated the residue was poured onto crushed ice Ammonium hydroxide was added till a pH of 8 The product was extracted with trichloromethane The extract was dried filtered evaporated The residue was purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (95:5 by volume) as eluent The pure fractions were collected the eluent was evaporated The residue was crystallized from a mixture of 2,2'-oxybispropane and 2-propanol

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

実験手順: A solution of 49.86 g (0.6 mole) of 3-aminopyrazole and 84.56 g (0.66 mole) of α-acetyl-γ-butyrolactone dissolved in 60 ml of N,N-dimethylformamide was heated under reflux for 2 hours. At the end of this time, the reaction mixture was cooled to room temperature, after which 100 ml of ethanol was added to it and the precipitated crystals were collected by filtration. They were then washed with ethanol to afford 104.9 g (yield 90%) of the title compound as prisms, melting at 225°-226° C. was heated under reflux for 2 hours the precipitated crystals were collected by filtration They were then washed with ethanol