trimethylsilylmethanol

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

実験手順: 8.5 g (0.1 mole) of cyanoacetic acid, 10.43 g (0.1 mole) of trimethylsilylmethanol, 30.66 g (0.12 mole) of 2-chloro-1-methylpyridinium iodide, 24.3 g (0.24 mole) of triethylamine and 200 ml of tetrahydrofuran were placed in a reaction vessel and reaction was allowed to take place at 50° C. for 3 hours in an argon atmosphere. Thereafter, a 10% aqueous sodium thiosulfate solution was added, followed by extraction with ether. An organic layer obtained was washed with a 10% aqueous sodium thiosulfate solution and then with water, then dried overnight with anhydrous magnesium. Thereafter, the desiccant was filtered off and the solvent was removed under a reduced pressure, followed by vacuum distillation to afford 14.6 g of trimethylsilylmethyl α-cyanoacetate (NCCH2CO2CH2SiMe3) (b.p. 81°-82° C./2 mmHg, yield 85%). reaction at 50° C. for 3 hours followed by extraction with ether An organic layer obtained was washed with a 10% aqueous sodium thiosulfate solution with water, then dried overnight with anhydrous magnesium Thereafter, the desiccant was filtered off the solvent was removed under a reduced pressure followed by vacuum distillation

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

実験手順: 33 g (0.41 mole) of pyridine are slowly added dropwise to a mixture of 109 g (0.41 mole) of the S-enantiomer of tosyloxy-propionic acid chloride, 43.4 g (0.41 mole) of trimethylsilyl-methanol and 250 ml of toluene at 20° C., with stirring. The mixture is subsequently stirred at room temperature for 24 hours. Working up is then carried out by a procedure in which the reaction mixture is poured into water and extracted with toluene and the organic phase is concentrated by stripping off the diluent under reduced pressure. 130 g (96% of theory) of the S-enantiomer of trimethylsilyl-methyl 2-tosyloxy-propionate are obtained in this manner in the form of an oily product. The mixture is subsequently stirred at room temperature for 24 hours extracted with toluene the organic phase is concentrated

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

実験手順: In a reactor fitted with a Dean-Stark apparatus hydroxymethyltrimethylsilane (3.8 g, 0.036 mol) and cyanoacetic acid (3.1 g, 0.036 mol) in 50 ml of toluene are refluxed for 4 hours in the presence of one drop of concentrated sulfuric acid. The organic phase is washed twice with water and is dried over sodium sulfate. It is concentrated under reduced pressure. Distillation under vacuum (b.p. 80° C. under 0.4 hPa) gives 4.3 g (69% yield) of trimethylsilanylmethyl cyanoacetate in the form of a colorless liquid which is used as it is in the following step. The organic phase is washed twice with water is dried over sodium sulfate It is concentrated under reduced pressure Distillation under vacuum (b.p. 80° C. under 0.4 hPa)

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

実験手順: In a reactor fitted with a Dean-Stark apparatus hydroxymethyltrimethylsilane (3.8 g, 0.036 mol) and cyanoacetic acid (3.1 g, 0.036 mol) in 50 ml of toluene are refluxed for 4 hours in the presence of one drop of concentrated sulfuric acid. The organic phase is washed twice with water and is dried over sodium sulfate. It is concentrated under reduced pressure. Distillation under vacuum (b.p. 80° C. under 0.4 hPa) gives 4.3 g (69% yield) of trimethylsilanylmethyl cyanoacetate in the form of a colorless liquid which is used as it is in the following step. The organic phase is washed twice with water is dried over sodium sulfate It is concentrated under reduced pressure Distillation under vacuum (b.p. 80° C. under 0.4 hPa)

反応条件: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In 60 ml of N,N-dimethylformamide were dissolved 20 g of trimethylsilylmethanol. This was maintained at 5° C. in a water bath and 4.6 g of sodium hydride were added thereto in the atmosphere of argon. The resulting mixture was stirred at 5° C. for 1 hour. Thereafter, 33.3 g of 3-nitrophthalonitrile dissolved in 160 ml of N,N-dimethylformamide were added dropwise to the mixture. After completion of the addition, the ice bath was removed and the mixture was stirred at room temperature for 24 hours. The reaction product was then added with 200 ml of dilute hydrochloric acid and extracted with 1 liter of toluene. The organic layer was washed well with water, followed by the removal of water with magnesium sulfate and the purification with a toluene/silica gel column. However, the desired compound shown by the above formula (XV) was hardly obtained. The yield was about 1% and 3-methoxyphthalonitrile as a by-product was yielded in an amount of several times that of the compound (XV). were added dropwise to the mixture After completion of the addition the ice bath was removed the mixture was stirred at room temperature for 24 hours The reaction product was then added with 200 ml of dilute hydrochloric acid extracted with 1 liter of toluene The organic layer was washed well with water followed by the removal of water with magnesium sulfate the purification with a toluene/silica gel column was hardly obtained

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

実験手順: Acetyl chloride (0.59 g, 7.5 mmol) was added to trimethylsilylmethanol (4.03 g, 37.5 mmol) with stirring at room temperature. After 0.5 h, 5-{2-[2-(3-chloro-phenyl)-2-hydroxy-ethylamino]-propyl}-benzo[1,3]dioxole-2,2-dicarboxylic acid (1.05 g, 2.5 mmol) was added in portions. The resulting solution was stirred for 3 days, and then treated with 50 ml of 50% sodium bicarbonate solution, followed by extraction with ethyl acetate (50 ml). The organic extract was dried over anhydrous sodium sulfate, filtered, and evaporated. The residue was passed through a pad of silica gel, eluting with hexanes, and ether-hexanes/1:1 until no more trimethylsilylmethanol could be detected. The filter pad was then eluted with ethyl acetate, and the solvent was evaporated to give 1.14 g of the desired product as a colorless gum. Conversion to the HCl salt yielded 1.16 g of white foam; 1H NMR (CDCl3) δ 0.06 (s, 18H), 1.33 (d, J=6.5 Hz, 3H), 2.80 (m, 1H), 3.15 (m, 1H), 3.20 (m, 1H), 3.48 (m, 2H), 4.014 (s, 2H), 4.015 (s, 2H), 5.45 (bd, J=9.7 Hz, 1H), 5.60 (bs, 1H), 6.80 (m, 3H), 7.25 (m, 2H), 7.45 (s, 1H), 8.70 (bs, 1H), 10.10 (bs, 1H); IR (KBr): 1763 cm-1 (C=O); MS (ES) m/z 594 (MH+); [α]D25 -23° (c, 1.0, CHCl3). Anal. Calcd. for C28H40ClNO7Si2 ·HCl: C, 53.32; H, 6.39; N, 2.22; Cl, 11.24; Si, 8.91. Found: C, 52.65; H, 6.70; N, 2.11; Cl, 11.47; Si, 9.00. The resulting solution was stirred for 3 days followed by extraction with ethyl acetate (50 ml) The organic extract was dried over anhydrous sodium sulfate filtered evaporated eluting with hexanes, and ether-hexanes/1:1 until no more trimethylsilylmethanol The filter pad was then eluted with ethyl acetate the solvent was evaporated

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

実験手順: 8.5 g (0.1 mole) of cyanoacetic acid, 10.43 g (0.1 mole) of trimethylsilylmethanol, 30.66 g (0.12 mole) of 2-chloro-1-methylpyridinium iodide, 24.3 g (0.24 mole) of triethylamine and 200 ml of tetrahydrofuran were placed in a reaction vessel and reaction was allowed to take place at 50° C. for 3 hours in an argon atmosphere. Thereafter, a 10% aqueous sodium thiosulfate solution was added, followed by extraction with ether. An organic layer obtained was washed with a 10% aqueous sodium thiosulfate solution and then with water, then dried overnight with anhydrous magnesium. Thereafter, the desiccant was filtered off and the solvent was removed under a reduced pressure, followed by vacuum distillation to afford 14.6 g of trimethylsilylmethyl α-cyanoacetate (NCCH2CO2CH2SiMe3) (b.p. 81°-82° C./2 mmHg, yield 85%). reaction at 50° C. for 3 hours followed by extraction with ether An organic layer obtained was washed with a 10% aqueous sodium thiosulfate solution with water, then dried overnight with anhydrous magnesium Thereafter, the desiccant was filtered off the solvent was removed under a reduced pressure followed by vacuum distillation