tetrabutylazanium;fluoride;trihydrate

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

实验步骤: 4.71 g (10.26 mmol) of (rac.) 4-(4-chloro-3-fluoro-2-methoxyphenyl)-4-methyl-2-(trifluoromethyl)-2-trimethylsilyloxy-pentanoic acid ethyl ester is dissolved in 57 ml of tetrahydrofuran and mixed with 3.24 g (10.26 mmol) of tetrabutylammonium fluoride trihydrate: after stirring over the weekend at room temperature, the reaction mixture is mixed with water and extracted three times with methyl-tert-butyl ether. The combined organic extracts are washed with brine. After drying, the solvent is spun off, and the remaining residue is chromatographed on silica gel (mobile solvent ethyl acetate/hexane). 3.07 g (77.4%) of the desired compound is isolated. extracted three times with methyl-tert-butyl ether The combined organic extracts are washed with brine After drying the remaining residue is chromatographed on silica gel (mobile solvent ethyl acetate/hexane)

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

实验步骤: 4.4 g (9.67 mmol) of (rac.) 4-(3-chloro-2-methoxy-4-methylphenyl)-4-methyl-2-(trifluoromethyl)-2-trimethylsilyloxy-pentanoic acid ethyl ester is dissolved in 56 ml of tetrahydrofuran and mixed with 3.05 g (9.67 mmol) of tetrabutylammonium fluoride trihydrate and stirred for one and one-half hours at room temperature. The reaction mixture is diluted with water and extracted twice with diethyl ether. The organic phases are washed with water and with brine. After drying, the solvent is spun off, and the remaining residue is chromatographed on silica gel (mobile solvent ethyl acetate/hexane). 1.26 g of the desired compound is isolated. extracted twice with diethyl ether The organic phases are washed with water and with brine After drying the remaining residue is chromatographed on silica gel (mobile solvent ethyl acetate/hexane)

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Dissolve tetrabutylammonium fluoride trihydrate (0.436 g, 1.36 mmol) in 5 ml of acetonitrile. Add water (0.05 ml. 2.72 mmol) and stir for 10 minutes. Add trans-methanesulfonic acid 4-{(R)-3-[3,5-dichloro-4′-(4-trifluoromethyl-piperidine-1-carbonyl)-biphenyl-4-ylmethyl]-2-oxo-pyrrolidin-1-yl}-cyclohexyl ester (0.458 g, 0.68 mmol). Stir at 80° C. for 12 hours. Quench with saturated aqueous sodium bicarbonate and extract with ethyl acetate. Wash the extract with brine. Dry the organic layer over magnesium sulfate, filter, and concentrate under vacuum. Purify by silica gel chromatography recover 0.036 g (9%) of the title compound: MS (m/z): 579 (M+). Quench with saturated aqueous sodium bicarbonate extract with ethyl acetate Wash the extract with brine Dry the organic layer over magnesium sulfate filter concentrate under vacuum Purify by silica gel chromatography recover 0.036 g (9%) of the title compound

反应条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of E-4-t-butyldiphenylsilyloxy-1,3-butadienyl phosphonic diethyl ester (11 g, 26.4 mmol) and tetrabutylammonium fluoride trihydrate (10 g, 31 mmol) in tetrahydrofuran (100 ml) is stirred 2 hours at 20° C. The reaction mixture is concentrated in vacuo, diluted with ethyl acetate and washed with brine. The title product is obtained by flash chromatography on silica gel (4.6 g, 80%). The reaction mixture is concentrated in vacuo diluted with ethyl acetate washed with brine

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

实验步骤: 30.00 g of bicyclohexyl-4,4′-dione and 3.89 g of tetrabutylammonium fluoride trihydrate are dissolved in 350 ml of THF, and 30.33 g of trimethylsiylacetylene are added dropwise at RT. The reaction mixture is stirred for 2 days, a suspension of 44.86 g of potassium fluoride in 160 ml of methanol is subsequently added, and the mixture is stirred for a further 3 days. Conventional work-up gives 4,4′-diethynylbicyclohexyl-4,4′-diol. 30.33 g of trimethylsiylacetylene are added dropwise at RT is subsequently added the mixture is stirred for a further 3 days

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

实验步骤: 24.32 ml of (trimethylsilyl)acetylene are added dropwise at −30° C. to a solution of 30.0 g of 4′-propylbicyclohexyl-4-one and 3.41 g of tetrabutylammonium fluoride trihydrate in 300 ml of THF. The cooling bath is removed after 5 minutes, and the reaction mixture is stirred at RT for 2 hours. A suspension of 39.2 g of potassium fluoride in methanol is subsequently added, and the mixture is stirred at RT for 3 days. Conventional work-up gives 4-ethynyl-4′-propylbicyclohexyl-4-ol. The cooling bath is removed after 5 minutes A suspension of 39.2 g of potassium fluoride in methanol is subsequently added the mixture is stirred at RT for 3 days

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

实验步骤: 754 mg of (3R,4R)-4-(Biphenyl-4-ylcarbonyloxy)-3-[4-(tert-butyl-dimethyl-silanyloxy)-benzoylamino]-azepane-1-carboxylic acid tert-butyl ester were dissolved in 10 ml tetrahydrofuran and 147 mg of tetrabutylammoniumfluoride trihydrate were added at 0° C. and the reaction mixture was stirred for two hours at room temperature. 2.5 ml of a saturated solution of sodium chloride and 2.5 ml of an aqueous 1 molar solution of citric acid were added. The organic layer was concentrated under vacuo diluted with ethyl acetate then washed with 5 ml of a saturated solution of sodium chloride dried over magnesium sulfate and evaporated. The crude compound was purified on silica gel (dichloromethane:ethylacetate 1:1) to yield 551 mg (89% yield) of (3R,4R)-4-(Biphenyl-4-ylcarbonyloxy)-3-(4-hydroxy-benzoylamino)-azepane-1-carboxylic acid tert-butyl ester. The organic layer was concentrated under vacuo diluted with ethyl acetate then washed with 5 ml of a saturated solution of sodium chloride dried over magnesium sulfate evaporated The crude compound was purified on silica gel (dichloromethane:ethylacetate 1:1)

反应条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2 g of 4-[5-(4-Fluorophenyl)-1-(4-fluorophenylamino)-5-hydroxy-2-(2-oxo-4-phenyl-oxazolidine-3-carbonyl)-pentyl]-benzonitrile were dissolved in 20 ml of methyl-tert-butyl ether and, together with 100 mg of tetrabutylammonium fluoride trihydrate and 1.3 ml of bistrimethylsilyl acetamide, heated at 40° C. for about 1 h. The reaction was monitored by thin-layer chromatography. After the reaction ended, 0.2 ml of glacial acetic acid were initially added and the mixture was stirred for 30 min and then concentrated. 20 ml of a mixture of isopropanol/2N sulfuric acid=10:1 were added to the residue, and the mixture was stirred for 1 hour. Following addition of a spatula tip of solid sodium bicarbonate, the mixture was again concentrated under reduced pressure. The residue was taken up in ethyl acetate and the organic phase was washed with water and dried. The residue was, after removal of the solvent, purified by column chromatography (SiO2, CH2Cl2/methanol=100:1). This gave the product of molecular weight 418.45 (C25H20F2N2O2); MS (DCI+): 419 (M+H+). concentrated 20 ml of a mixture of isopropanol/2N sulfuric acid=10:1 were added to the residue the mixture was stirred for 1 hour addition of a spatula tip of solid sodium bicarbonate the mixture was again concentrated under reduced pressure the organic phase was washed with water dried after removal of the solvent purified by column chromatography (SiO2, CH2Cl2/methanol=100:1) This gave the product of molecular weight 418.45 (C25H20F2N2O2)

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

实验步骤: To a stirred solution of tert-butyl (S)-3-methyl-1-((S)-2,2,2-trifluoro-1-(3-(7-(2-methoxyethoxy)quinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)ethyl)pyrrolidin-3-ylcarbamate (1.37 g, 1.94 mmol) in THF (100 mL) was added tetrabutylammonium fluoride trihydrate (1.84 g, 5.83 mmol). The reaction mixture was stirred at ambient temperature for 2 hours. The mixture was partitioned between saturated aqueous NH4Cl solution and EtOAc. The aqueous layer was extracted with EtOAc. The combined organic layers were washed with water and brine, dried and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (3% MeOH in EtOAc) to give tert-butyl (S)-1-((R)-2,2,2-trifluoro-1-(3-(6-fluoro-7-(2-hydroxyethoxy)quinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)ethyl)pyrrolidin-3-ylcarbamate (1.01 g, 88%) as a white solid. The mixture was partitioned between saturated aqueous NH4Cl solution and EtOAc The aqueous layer was extracted with EtOAc The combined organic layers were washed with water and brine dried concentrated under reduced pressure The residue was purified by flash chromatography on silica gel (3% MeOH in EtOAc)

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

实验步骤: Trifluoromethyltrimethylsilane (2N in THF, 0.76 mL, 1.5 mmol) was added at 0° C. to a solution of 1-(2-methyl-pyridin-4-yl)-2-phenyl-propan-1-one (142 mg, 0.63 mmol) in THF (5 mL), followed by the addition of tetrabutylammonium fluoride trihydrate (40 mg, 0.13 mmol). After stirring overnight at r.t., an additional amount of trifluoromethyl-trimethylsilane (0.38 mL), followed by tetrabutylammonium fluoride trihydrate (20 mg) was added to drive the reaction towards completion. The solvent was evaporated, the residue was taken up in methanol, and the title compound (42 mg, 23%) was isolated by reversed-phase, preparative HPLC (Agilent Zorbax XdB-C18 column, solvent gradient 5-95% CH3CN in 0.1% TFA[aq]). 1H NMR (300 MHz, DMSO-D6) 8.25 (1H, d), 7.17 (1H, s), 7.11 (2H, d), 7.09-7.00 (4H, m), 6.93 (1H, s), 3.62 (1H, q), 2.35 (3H, s), 1.42 (3H, d); MS (m/e)=296.4 [MH+]. was added the reaction towards completion The solvent was evaporated

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

实验步骤: Trifluoromethyltrimethylsilane (2N in THF, 0.6 mL, 1.2 mmol) was added at 0° C. to a solution of 2-(2-chloro-4-methoxy-phenyl)-1-(5-methyl-pyrazin-2-yl)-propan-1-one (290 mg, 1.0 mmol) in THF (7 mL), followed by the addition of tetrabutylammonium fluoride trihydrate (31 mg, 0.1 mmol). After stirring overnight at r.t., the title compound (87 mg, 24%) was isolated from the reaction mixture by reversed-phase, preparative HPLC (Agilent Zorbax XdB-C18 column, solvent gradient 5-95% CH3CN in 0.1% TFA[aq]). 1H NMR (300 MHz, CDCl3) 8.75 (1H, s), 8.13 (1H, s), 7.44 (1H, d), 6.64 (1H, d), 6.59 (1H, dd), 5.90 (1H, s), 4.33 (1H, q), 3.67 (3H, s), 2.50 (3H, s), 1.54 (3H, d); MS (m/e, ISP neg. ion)=359.1 [M−H+].

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

实验步骤: Compounds 3′,5′-O-bis-(tert-butyldimethylsilyl)-5-(2-isopropylbenzyloxy)methyl-2′-deoxyuridine (134 mg, 0.22 mmol) and (3′ or 5′)-O-(tert-butyldimethylsilyl)-5-(2-isopropylbenzyloxy)methyl-2′-deoxyuridine (98 mg, 0.19 mmol) were dissolved in THF (5 mL), and a solution of tetra-n-butylammonium fluoride trihydrate (323 mg, 1.05 mmol) in THF (2 mL) was added. The mixture was stirred at room temperature for one hour, then concentrated in vacuo and purified by silica gel column chromatography to give 5-(2-isopropylbenzyloxy)methyl-2′-deoxyuridine dU.n6 (108 mg, 67%). concentrated in vacuo purified by silica gel column chromatography