| 93% |
With 1H-imidazole; In dichloromethane; at 0 - 20℃; for 6h; |
To a solution of methyl (R)-2-hydroxylpropanoate 12 (2 g, 19.21 mmol) in dry DCM (60 mL) was added imidazole (1.96 g, 28.815 mmol), and the mixture was stirred for 10 min at 0 C. To this solution tert-butyldimethylsilyl chloride (3.47 g, 23.05 mmol) was added at 0 C and the mixture was stirred at room temperature for 6 h. After completion of the reaction, the mixture was diluted with cold water and extracted into DCM (3 × 75 mL). The combined extract was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude residue was purified by column chromatography using hexane/ethyl acetate (97:3) to give pure 13 (3.9 g, 93%) as a colorless oil. (c 2.8, CHCl3) [Lit.15b +27.2 (c 1.89, CCl4)]; IR (neat, cm-1): numax 2944, 2894, 2859, 1753, 1255, 1146, 838, 778; 1H NMR (300 MHz, CDCl3): delta 4.25 (q, J = 6.8 Hz, 1H), 3.67 (s, 3H), 1.35 (d, J = 6.8 Hz, 3H), 0.87 (s, 9H), 0.04 (d, J = 7.7 Hz, 6H); 13C NMR (75 MHz, CDCl3): delta 172.6, 67.5, 50.6, 25.0, 20.5, 17.5, -5.6, -6.0; ESI/MS (m/z): 241 (M+Na+). |
| 85% |
With 1H-imidazole; In N,N-dimethyl-formamide; at 20℃; for 18h;Inert atmosphere; |
To a solution of (R)-(+)-methyl lactate (2.95 g, 28.34 mmol) in DMF (20 mL) was added tert-butyldimethyl silyl chloride (6.41 g, 42.51 mmol) and imidazole (6.75 g, 99.18 mmol). After stirring at a room temperature for 18 hr, the reaction mixture was diluted with a saturated aqueous NaCl solution (90 mL) and extracted with petroleum ether (3×60 mL). The organic layer was washed with a cold 3% HCl solution (30 mL) and a saturated aqueous NaCl solution (30 mL), dried over Na2SO4 and concentrated. The remaining residue was purified by silica gel (105 g) with petroleum ether (300 mL), followed by 3% ethyl acetate in petroleum ether (600 mL). The 3% ethyl acetate in the petroleum ether fractions was collected and the solvent was removed to give 5.26 g of (R)-(+)-Methyl 2-(tert-butyldimethylsilyloxy)propanoate as colorless oil (85% yield). 1H NMR (CDCl3): delta 4.26 (q, 1H, J=6.8 Hz, -CH), 3.65 (s, 3H, -OCH3), 1.32 (d, 3H, J=6.8 Hz, -CH3), 0.83 (s, 9H, Si-(CH3)3), 0.03 (s, 3H, Si-CH3), 0.00 (s, 3H, Si-CH3). |
| 67% |
With 1H-imidazole; In dichloromethane; at 0 - 20℃; for 2h; |
Step la: methyl (2R)-2-[(tert-butyIdimethyIsiIyl)oxy]propanoate: into a 250-mL round-bottom flask, was placed a solution of methyl (2R)-2-hydroxypropanoate (5 g, 48.03 mmol, 1 .00 equiv) and Imidazole (6.5 g, 95.59 mmol, 2.00 equiv) in dichloromethane (100 mL). This was followed by the addition of a solution of tert-butyl(chloro)dimethylsilane (8.7 g, 57.72 mmol, 1.20 equiv) in dichloromethane (50 mL) dropwise with stirring at 0 C. The resulting solution was stirred for 2 hours at room temperature. The reaction was then quenched by the addition of 100 mL of water/ice. The resulting solution was extracted with dichloromethane (3x100 mL) and the organic layers combined. The resulting mixture was washed with brine (3x50 mL), dried over anhydrous sodium sulfate and concentrated under vacuum. This resulted in 7 g (67%) of methyl (2R)-2-[(tert-butyldimethylsilyl)oxy]propanoate as colorless oil. |
| 67% |
With 1H-imidazole; In dichloromethane; at 0 - 20℃; for 2h; |
into a 250-mL round-bottom flask was placed a solution of methyl (2/?)-2-hydroxypropanoate (5 g, 48.03 mmol, 1.00 eq.) and imidazole (6.5 g, 95.59 mmol, 2.00 eq.) in dichloromethane (100 mL), followed by the dropwise addition of a solution of tert-butyl(chloro)dimethylsilane (8.7 g, 57.72 mmol, 1.20 eq.) in dichloromethane (50 mL) at 0 C. The resulting solution was stirred for 2 h at room temperature. The reaction was quenched by the addition of 100 mL of water/ice. The resulting solution was extracted with dichloromethane (3 x 100 mL) and the organic layers combined. The resulting mixture was washed with brine (3 x 50 mL), dried over anhydrous sodium sulfate and concentrated under vacuum to afford 7 g (67%) of methyl (2R)- 2-[(tert-butyldimethylsilyl)oxy]propanoate as a colorless oil |
| 67% |
With 1H-imidazole; In dichloromethane; at 0 - 20℃; for 2h; |
into a 250-mL round-bottom flask, was placed a solution of methyl (2R)-2-hydroxypropanoate (5 g, 48.03mmol, 1.00 equiv) and Imidazole (6.5 g, 95.59 mmol, 2.00 equiv) in dichloromethane (100 mL). This was followed by the addition of a solution of tert-butyl(chloro)dimethylsilane (8.7 g, 57.72 mmol, 1.20 equiv) in dichloromethane (50 mL) dropwise with stirring at 0 C. The resulting solution was stirred for 2 hours at room temperature. The reaction was then quenched by the addition of 100 mL of water/ice. The resulting solution was extracted withdichloromethane (3x100 mL) and the organic layers combined. The resulting mixture waswashed with brine (3x50 mL), dried over anhydrous sodium sulfate and concentrated under vacuum. This resulted in 7 g (67%) of methyl (2R)-2-[(tert-butyldimethylsilyl)oxy]propanoate as colorless oil. |
| 67% |
With 1H-imidazole; In dichloromethane; at 0 - 20℃; for 2h; |
into a 250-mL round-bottom flask, was placed a solution of methyl (2R)-2-hydroxypropanoate (5 g, 48.03mmol, 1.00 equiv) and imidazole (6.5 g, 95.59 mmol, 2.00 equiv) in dichloromethane (100 mL). This was followed by the addition of a solution of tert-butyl(chloro)dimethylsilane (8.7 g, 57.72 mmol, 1.20 equiv) in dichloromethane (50 mL) dropwise with stirring at 0 C. The resulting solution was stirred for 2 hours at room temperature. The reaction was then quenched by the addition of 100 mL of water/ice. The resulting solution was extracted with dichloromethane (3 x 100 mL) and the organic layers combined. The resulting mixture was washed with brine (3 x 50 mL), dried over anhydrous sodium sulfate and concentrated undervacuum to give 7 g (67%) of methyl (2R)-2-[(tert-butyldimethylsilyl)oxyjpropanoate as colorless oil. |
| 67% |
With 1H-imidazole; In dichloromethane; at 0 - 20℃; for 2h; |
into a 250-mLround-bottom flask was placed a solution of methyl (2R)-2-hydroxypropanoate (5 g, 48.03mmol, 1.00 eq.) and imidazole (6.5 g, 95.59 mmol, 2.00 eq.) in dichloromethane (100 mL), followed by the dropwise addition of a solution of tert-butyl(chloro)dimethylsilane (8.7 g, 57.72 mmol, 1.20 eq.) in dichloromethane (50 mL) at 0 C. The resulting solution was stirred for 2 h at room temperature. The reaction was quenched by the addition of 100 mL ofwater/ice. The resulting solution was extracted with dichloromethane (3 x 100 mL) and the organic layers combined. The resulting mixture was washed with brine (3 x 50 mL), dried over anhydrous sodium sulfate and concentrated under vacuum to afford 7 g (67%) of methyl (2R)- 2-[(tert-butyldimethylsilyl)oxyjpropanoate as a colorless oil. |
| 67% |
With 1H-imidazole; In dichloromethane; at 0 - 20℃; for 2h; |
into a 250- mL round-bottom flask was placed a solution of methyl (2R)-2-hydroxypropanoate (5 g, 48.03 mmol, 1.00 eq.) and imidazole (6.5 g, 95.59 mmol, 2.00 eq.) in dichloromethane (100 mL), followed by the dropwise addition of a solution of tert-butyl(chloro)dimethylsilane (8.7 g, 57.72 mmol, 1.20 eq.) in dichloromethane (50 mL) at 0 C. The resulting solution was stirred for 2 h at room temperature. The reaction was quenched by the addition of 100 mL of water/ice. The resulting solution was extracted with dichloromethane (3 x 100 mL) and the organic layers combined. The resulting mixture was washed with brine (3 x 50 mL), dried over anhydrous sodium sulfate and concentrated under vacuum to afford 7 g (67%) of methyl (2R)-2-[(tert-butyldimethylsilyl)oxy]propanoate as a colorless oil. |
|
With 1H-imidazole; In dichloromethane; at 0 - 20℃; for 21h; |
A dry 500 mL flask was charged with imidazole (6.53 g, 96.0 mmol, 2 equiv) and DCM (240 mL) before it was cooled to 0 C. Once cool, (R)-methyl 2-hydroxypropanoate (5 g, 48.0 mmol, 1 equiv) and TBSC1 (9.40 g, 62.4 mmol, 1.3 equiv) were added to the solution sequentially, and the resulting mixture was allowed to warm to room temperature. After stirring for 21 hours, the reaction mixture was filtered, and the solid residue was washed with DCM. The combined filtrate was washed with 1 M HC1 (100 mL), saturated aqueous sodium bicarbonate (100 mL), and brine (100 mL), sequentially. The washed organic solution was then dried over sodium sulfate, filtered, and concentrated to give methyl (R)-2-((tert- butyldimethylsilyl)oxy)propanoate as a clear, colorless oil (10.4 g, 100% yield). This material was carried into the next step without further characterization or purification |
|
With dmap; triethylamine; In dichloromethane; at 20℃; for 16h;Cooling with ice; |
Step 1: methyl (R)-2-((tert-butyldimethylsilyl)oxy)propanoate TEA (5.82 mL, 43 mmol) and DMAP (0.35 g, 2.88 mmol) were added sequentially to an ice-cooled solution of (+) D-Methyl lactate (3 g, 28.8 mmol) in DCM (60 mL). To the resulting reaction mixture was added a solution of tert-Butyldimethylsilyl chloride (4.75 g, 31.6 mmol) in DCM (15 mL) and the reaction mixture was stirred for 16 h at room temperature, then diluted with water (70 mL) and organic layer was separated off. The organic layer was washed with 1M citric acid solution (50 mL) followed by saturated sodium bicarbonate solution (50 mL) and dried over anhydrous Na2SO4 Solvent was removed under reduced pressure to afford the product (4.78 g, 78%) as colorless oil which was used as such without further purification. 1H NMR (400 MHz, CDCl3): delta 4.31 (q, J=6.7 Hz, 1H), 0.90 (s, 1H), 0.89 (s, 9H), 0.09 (s, 3H), 0.07 (s, 3H), LC-MS: [M+H]+ 218.9. |
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