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With triethylamine; In dichloromethane; |
a) Firstly 1.46 ml (0.0105 mol) of triethylamine and then 1.7 ml (0.0102 mol) of trifluoromethanesulphonic anhydride were added dropwise under argon to an ice-cold solution of 2.49 g (0.010 mol) of tert.-butyl 6-hydroxy-3,4-dihydro-1H-isoquinoline-2-carboxylate in 80 ml of dichloromethane. The mixture was stirred at room temperature for 1 hour, poured into saturated sodium hydrogen carbonate solution, extracted with ethyl acetate and completely freed from the solvents. 3.81 g of oily crude tert.-butyl 6-(trifluoromethanesulphonyloxy)-3,4-dihydro-1H-isoquinoline-2-carboxylate were obtained. |
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To a solution of 6-hydroxy-3,4-dihydro-lH-isoquinoline-2-carboxylic acid tert-butyl ester (12.46 g, 50 mmol) in anhydrous DCM (150 ml) cooled to 0 0C is added TEA (10.45 ml, 75 mmol, 1.5 eq.), <n="44"/>followed by the addition of trifluoromethanesulfonic anhydride (15.51 g, 55 inmol, 1.1 eq.) dropwise. After the addition is completed, 4-dimethylaminopyridine is added (100 mg). The reaction mixture is stirred at 0 0C for 1 h, then warmed to it, and stirred for an additional 1 h. Water (200 ml) is added to quench the reaction. The DCM layer is collected, washed with water and brine, and dried over sodium sulfate, and the solvent is removed under reduced pressure. Purification of the residue through silica gel flash chromatography (hexane/EA 10:1) gives the title compound. |
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With triethylamine; In dichloromethane; at 0 - 20℃; |
To a solution of <strong>[158984-83-9]1,1-dimethylethyl 6-hydroxy-3,4-dihydro-2(1H)-isoquinolinecarboxylate</strong> (4.92 g; 19.8 mmol, as per step 2 above) and Et3N (3.31 mL; 23.8 mmol) in CH2Cl2 at 0 C. was added Tf2O (3.65 mL; 21.7 mmol), dropwise over 3 minutes. The mixture was slowly warmed to room temperature (overnight), poured into water and the layers were separated. The aqueous layer was extracted with CH2Cl2 (×2), combined organics were washed (water, brine), dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash chromatography (EtOAc/hexanes), affording the title compound as a colorless gum which gradually solidified. 1H NMR (400 MHz, CDCl3) delta 1.49 (s, 9H), 2.87 (t, J=5.7 Hz, 2H), 3.66 (br. t, J=5.5 Hz, 2H), 4.59 (s, 2H), 7.04-7.12 (m, 2H), 7.18 (d, J=8.4 Hz, 1H). |
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With triethylamine; In dichloromethane; at 0℃; |
To a solution of <strong>[158984-83-9]1,1-dimethylethyl 6-hydroxy-3,4-dihydro-2(1H)-isoquinolinecarboxylate</strong> (0.146 g; 0.586 mmol) and Et3N (0.17 mL; 1.2 mmol) in CH2Cl2(5 mL) at 0 C. was added Tf2O (0.11 mL; 0.67 mmol (dropwise over 2 min. The mixture was stirred overnight, gradually warming to room temperature, diluted with CH2Cl2, washed (water, brine), dried over Na2SO4and concentrated in vacuo. The residue was purified by flash chromatography (EtOAc/hexanes), affording the title compound as a colorless gum which slowly solidified. |
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With pyridine; In dichloromethane; at 0℃; for 1h; |
To a solution of pyridine (16.22 ml, 201 mmoi) and tert-butyi6-hydroxy-3,4-dihydroisoquinoline-2(1l-{)-carboxylate (50.0 g, 201 mmol) in DCM (600 ml), Tf2.O (33.9 ml. 201 inmol) was added dropwise at 0C and the mixture was stirred at 0 C for I h. The reaction mixture was diluted with DCM (800 niL), washed with water (2 x200 mL) and brine (2 x 2CC mE). The organic solution was dried, filtered, concentrated in vacuo and purified by silica gel chromatography (PE:EtOAc=80: 1 ?1 0:1) to give the title compound. |
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To a solution of 6-hydroxy-3,4-dihydro-lH-isoquinoline-2-carboxylic acid tert-bxxty ester (12.46 g, 50 mmol) in anhydrous DCM (150 ml) cooled to 0 0C is added TEA (10.45 ml, 75 mmol, 1.5 eq.), followed by trifluoromethanesulfonic anhydride (15.51 g, 55 mmol, 1.1 <n="66"/>eq.) added dropwise. After the addition is complete, 4-dimethyIaminopyridine is added (100 mg). The reaction mixture is stirred at 0 0C for 1 hr, then warmed to rt and stirred for an additional 1 hr. Water (200 ml) is added to quench the reaction. The DCM layer is collected, washed with water and brine, and dried over sodium sulfate, and the solvent is removed under reduced pressure. Purification of the residue through silica gel flash chromatography (hexane/EtOAc 10:1) gives the title compound. MS (+VE) m/z 382.2 (M+ +1). |