2-(三甲基硅)苯基三氟甲烷磺酸盐

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: In a nitrogen atmosphere compound 20 (150 mg, 0.300 mmol) is suspended in Acetonitrile (4 ml). 2-(trimethylsilyl)phenyl trifluoromethanesulfonate (0.146 ml, 0.600 mmol) and CsF (182 mg, 1.200 mmol) are added and the mixture is stirred for 45 minutes at RT. Additional CsF (137 mg, 0.900 mmol) (not dried) is added and the mixture is stirred for 5 hours then it is poured in water. Acetonitrile is evaporated and the reaction mixture is partitioned between water and AcOEt. The organic layer is separated dried over Na2SO4 and concentrated. The crude is purified by silica gel flash chromatography (eluent DCM/MeOH 98/2) affording the title compound (49 mg, 0.091 mmol, 30.3% yield). is added the mixture is stirred for 5 hours Acetonitrile is evaporated the reaction mixture is partitioned between water and AcOEt The organic layer is separated dried over Na2SO4 concentrated The crude is purified by silica gel flash chromatography (eluent DCM/MeOH 98/2)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of tert-butyl 1,2,3,4-tetrahydroquinolin-3-ylcarbamate (0.3 g, 1.2 mmol) in acetonitrile (5 mL) was added 2-(trimethylsilyl)phenyl trifluoromethane sulfonate (397 mg, 1.33 mmol, 1.1 eq) and cesium fluoride (365 mg, 2.4 mmol, 2.0 eq). The mixture was stirred at room temperature for 3 days. Ethyl acetate was then added and the organic layer washed with brine, dried over sodium sulfate and evaporated. The residue was purified by flash column (eluted with 10% ethyl acetate in hexane) to give tert-butyl 1-phenyl-1,2,3,4-tetrahydroquinolin-3-ylcarbamate as a white solid (400 mg, 99%). M.p.=139-141° C. 1H NMR (DMSO) 400 MHz δ 7.33 (m, 2H), 7.18 (dd, J=1.2 and 7.6 Hz, 2H), 7.09-6.87 (m, 4H), 6.68-6.58 (m, 2H), 3.80 (s, br, 1H), 3.64 (m, 1H), 3.29 (m, 1H), 2.94 (dd, J=5.2 and 10.8 Hz, 1H), 2.72 (m, 1H), 1.34 (s, 9H). LCMS m/e 325 (M+H). the organic layer washed with brine dried over sodium sulfate evaporated The residue was purified by flash column (eluted with 10% ethyl acetate in hexane)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of indolin-5-yl 4-isopropylphenylcarbamate (50 mg, 0.17 mmol) in 3.4 mL of acetonitrile was added 2-(trimethylsilyl)phenyl trifluoromethanesulfonate (41 μL, 0.17 mmol) and caesium fluoride (51 mg, 0.34 mmol) at room temperature, successively. After the reaction mixture was stirred at the same temperature overnight, the reaction mixture was diluted with ethyl acetate. The organic layer was washed with water and brine, and dried over MgSO4. After filtration, the filtrate was concentrated in vacuo, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate=95/5 to 80/20) to obtain the title compound as a white solid (5.2 mg, 8%). The organic layer was washed with water and brine dried over MgSO4 After filtration the filtrate was concentrated in vacuo the residue was purified by silica gel column chromatography (hexane/ethyl acetate=95/5 to 80/20)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of indolin-5-yl 4-isopropylphenylcarbamate (50 mg, 0.17 mmol) in 3.4 mL of acetonitrile was added 2-(trimethylsilyl)phenyl trifluoromethanesulfonate (41 μL, 0.17 mmol) and caesium fluoride (51 mg, 0.34 mmol) at room temperature, successively. After the reaction mixture was stirred at the same temperature overnight, the reaction mixture was diluted with ethyl acetate. The organic layer was washed with water and brine, and dried over MgSO4. After filtration, the filtrate was concentrated in vacuo, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate=95/5 to 80/20) to obtain the title compound as a white solid (5.2 mg, 8%). The organic layer was washed with water and brine dried over MgSO4 After filtration the filtrate was concentrated in vacuo the residue was purified by silica gel column chromatography (hexane/ethyl acetate=95/5 to 80/20)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of indolin-5-yl 4-isopropylphenylcarbamate (50 mg, 0.17 mmol) in 3.4 mL of acetonitrile was added 2-(trimethylsilyl)phenyl trifluoromethanesulfonate (41 μL, 0.17 mmol) and caesium fluoride (51 mg, 0.34 mmol) at room temperature, successively. After the reaction mixture was stirred at the same temperature overnight, the reaction mixture was diluted with ethyl acetate. The organic layer was washed with water and brine, and dried over MgSO4. After filtration, the filtrate was concentrated in vacuo, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate=95/5 to 80/20) to obtain the title compound as a white solid (5.2 mg, 8%). The organic layer was washed with water and brine dried over MgSO4 After filtration the filtrate was concentrated in vacuo the residue was purified by silica gel column chromatography (hexane/ethyl acetate=95/5 to 80/20)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a suspension of compound 73 (11.97 g) in CH3CN (125 mL) was added 2-(trimethylsilyl)phenyl trifluoromethanesulfonate (75) (30 g) and CsF (20 g). The mixture was stirred at room temperature for 3 days. Water was added to quench the reaction and most of the CH3CN was removed via rotavaporator. The residue was extracted with EtOAc, washed with water and brine, and dried over MgSO4. After concentration of the solvent, the crude product was purified by silica gel chromatography, eluting with a gradient of 100% hexane to 80% EtOAc/hexane over 30 min. The pure product was isolated as a brown oil. 1H NMR (CDCl3) δ 7.30-7.24 (m 3H), 7.21-7.15 (m, 3H), 7.01 (dd, 1H, J=5.1, 9.6 Hz), 6.87 (d, 2H, J=8.7 Hz), 5.62 (d, 2H, J=9.6 Hz), 4.31 (d, 1H, J=5.1 Hz), 3.81 (s 3H), 1.65 (s, 3H). to quench the reaction most of the CH3CN was removed via rotavaporator The residue was extracted with EtOAc washed with water and brine dried over MgSO4 After concentration of the solvent, the crude product was purified by silica gel chromatography eluting with a gradient of 100% hexane to 80% EtOAc/hexane over 30 min The pure product was isolated as a brown oil

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of N-benzyl-2-(4-hydroxy-2-oxopyridin-1(2H)-yl)-4-methylthiazole-5-carboxamide (0.20 g, 0.58 mmol) and 2-(trimethylsilyl)phenyl trifluoromethanesulfonate (0.19 g, 0.64 mmol) in anhydrous acetonitrile (10 mL) was added cesium fluoride (0.22 g, 1.46 mmol). The reaction mixture was heated at 60° C. for 16 hours, followed by the addition of ethyl acetate (30 mL). The mixture was washed with saturated ammonium chloride (10 mL), dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated in vacuo. The residue was purified by column chromatography eluted with ethyl acetate/hexane (1/1) and further purified by recrystallization in ether to afford the title compound as a colorless solid in 14% yield (0.032 g): mp 67-70° C. (ether); 1H NMR (300 MHz, CDCl3) δ 8.76 (d, J=8.1 Hz, 1H), 7.45-7.25 (m, 8H), 7.11-7.08 (m, 2H), 6.35 (dd, J=8.1, 2.7 Hz, 1H), 6.05 (t, J=5.6 Hz, 1H), 5.81 (d, J=2.6 Hz, 1H), 4.58 (d, J=5.6 Hz, 2H), 2.69 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 167.8, 162.1, 161.8, 153.3, 152.8, 152.1, 137.7, 132.2, 130.3, 128.8, 127.9, 127.7, 126.4, 122.5, 121.1, 103.4, 100.2, 44.1, 17.3; MS (ES+) m/z 418.2 (M+1). The mixture was washed with saturated ammonium chloride (10 mL) dried over anhydrous sodium sulfate filtered the filtrate was concentrated in vacuo The residue was purified by column chromatography eluted with ethyl acetate/hexane (1/1) further purified by recrystallization in ether

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of tert-butyl ((3S,7S,8R,9S)-7-benzyl-8-hydroxy-9-methyl-2-oxo-1,5-dioxonan-3-yl)carbamate (500 mg, 1.32 mmol, 1.00 equiv) in anhydrous CH3CN (13 mL) were added 2-(trimethylsilyl)phenyl trifluoromethanesulfonate (0.480 mL, 1.98 mmol, 1.50 equiv) followed by CsF (500 mg, 3.29 mmol, 2.50 equiv). The resulting mixture was stirred at room temperature for 2 d. The reaction was then poured into ½ sat'd NaCl solution (20 mL), extracted with EtOAc (3×20 mL), and the combined organic extracts were dried over MgSO4, filtered, and concentrated to provide an oily yellow suspension. This was purified by automated silica gel column chromatograpy to provide tert-butyl ((3S,7S,8R,9S)-7-benzyl-9-methyl-2-oxo-8-phenoxy-1,5-dioxonan-3-yl)carbamate (69 mg, 11%) as an amorphous light yellow solid: 1H NMR (400 MHz, CDCl3) δ 7.34-7.20 (m, 5H), 7.20-7.04 (m, 4H), 7.02-6.88 (d, J=8.7 Hz, 4H), 5.20-5.02 (dq, J=9.1, 6.4 Hz, 2H), 4.71-4.57 (m, 1H), 4.37-4.21 (t, J=8.9 Hz, 1H), 4.00-3.88 (dd, J=11.6, 7.3 Hz, 1H), 3.60-3.44 (s, 2H), 3.38-3.21 (m, 1H), 3.07-2.93 (dd, J=13.6, 3.1 Hz, 1H), 2.37-2.21 (t, J=12.5 Hz, 1H), 2.22-2.09 (m, 1H), 1.46-1.40 (s, 9H), 1.40-1.34 (d, J=6.4 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 172.29, 159.20, 154.98, 139.50, 129.75, 129.11, 128.42, 126.19, 121.34, 115.48, 81.96, 80.19, 75.39, 72.88, 72.08, 52.98, 47.56, 35.29, 28.29, 18.98; ESIMS m/z 478.6 ([M+Na]+). extracted with EtOAc (3×20 mL) the combined organic extracts were dried over MgSO4 filtered concentrated to provide an oily yellow suspension This was purified by automated silica gel column chromatograpy

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Following the general procedure, treatment of isoquinoline (0.064 g, 59 μL, 0.50 mmol) and 3,4-dichlorobenzaldehyde (0.130 g, 0.75 mmol) with 2-(trimethylsilyl)phenyl trifluoromethanesulfonate (0.179 g, 146 μL, 0.60 mmol) in the presence of KF (0.070 g, 1.2 mmol) and 18-crown-6 (0.317 g, 1.2 mmol) in THF (2.0 mL) at −10° C. to room temperature for 12 hrs followed by flash column chromatography (Pet. ether/EtOAc=93/07) of the crude reaction mixture afforded 6-(3,4-dichlorophenyl)-4bH,6H-benzo[4,5][1,3]oxazino[2,3-a]isoquinoline as inseparable mixture of diastereomers as a yellow solid (0.146 g, 77% yield, dr determined by 1H NMR analysis of crude reaction mixture is 1:1). at −10° C. to room temperature for 12 hrs reaction mixture

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Following the general procedure, treatment of isoquinoline (00.064 g, 59 μL, 0.50 mmol) and 2-fluorobenzaldehyde (0.095 g, 79 μL, 0.75 mmol) with 2-(trimethylsilyl)phenyl trifluoromethanesulfonate (0.179 g, 146 μL, 0.60 mmol) in the presence of KF (0.070 g, 1.2 mmol) and 18-crown-6 (0.317 g, 1.2 mmol) in THF (2.0 mL) at −10° C. to room temperature for 12 hrs followed by flash column chromatography (Pet. ether/EtOAc=93/07) of the crude reaction mixture afforded 6-(2-fluorophenyl)-4bH,6H-benzo[4,5][1,3]oxazino[2,3-a]isoquinoline as inseparable mixture of diastereomers as a yellow solid (0.105 g, 64% yield, dr determined by 1H NMR analysis of crude reaction mixture is 3:1). at −10° C. to room temperature for 12 hrs reaction mixture

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Following the general procedure, treatment of isoquinoline (0.064 g, 59 μL, 0.50 mmol) and 3-bromobenzaldehyde (0.139 g, 884, 0.75 mmol) with 2-(trimethylsilyl)phenyl trifluoromethanesulfonate (0.179 g, 146 μL, 0.60 mmol) in the presence of KF (0.070 g, 1.2 mmol) and 18-crown-6 (0.317 g, 1.2 mmol) in THF (2.0 mL) at −10° C. to room temperature for 12 hrs followed by flash column chromatography (Pet. ether/EtOAc=93/07) of the crude reaction mixture afforded 6-(3-bromophenyl)-4bH,6H-benzo[4,5][1,3]oxazino[2,3-a]isoquinoline as inseparable mixture of diastereomers as a yellow solid (0.121 g, 62% yield, dr determined by 1H NMR analysis of crude reaction mixture is 3:2). at −10° C. to room temperature for 12 hrs reaction mixture

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Following the general procedure, treatment of isoquinoline (0.064 g, 59 μL, 0.50 mmol) and 4-fluorobenzaldehyde (0.093 g, 80 μL, 0.75 mmol) with 2-(trimethylsilyl)phenyl trifluoromethanesulfonate (0.179 g, 146 μL, 0.60 mmol) in the presence of KF (0.070 g, 1.2 mmol) and 18-crown-6 (0.317 g, 1.2 mmol) in THF (2.0 mL) at −10° C. to room temperature for 12 hrs followed by flash column chromatography (Pet. ether/EtOAc=93/07) of the crude reaction mixture afforded 6-(4-fluorophenyl)-4bH,6H-benzo[4,5][1,3]oxazino[2,3-a]isoquinoline as inseparable mixture of diastereomers as a yellow solid (0.151 g, 92% yield, dr determined by 1H NMR analysis of crude reaction mixture is 3:2). at −10° C. to room temperature for 12 hrs reaction mixture