被压抑-4-恩-1-ol

反应条件: temp:0.00; pressure:0.00; stir:

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

实验步骤: N-(t-Butoxycarbonyl)alanine (3.1 g, 1 eq) and DCM (50 mL) were added to a vessel with stirring followed by the addition of CDI (3.1 g, 1.15 eq). The mixture was stirred at ambient temperature for 18 h after which time 4-penten-1-ol (1.8 g, 1.25 eq) was added. The mixture was stirred a further 18 h at ambient temperature at which point the reaction was quenched with 1N HCl. A biphasic mixture was formed and the layers were separated. The organic layer was washed with saturated aqueous NaHCO3 solution and then concentrated to give pent-4-en-1-yl 2-((tert-butoxycarbonyl)amino)propanoate as an oil. The oil was dissolved in DCM (50 mL) and methanesulfonic acid (2.2 g, 1.4 eq) was added. The mixture was stirred at ambient temperature for ˜22 h then cooled in an ice/water bath. Ethyl 2-chloro-2-oxoacetate (3.4 g, 1.5 eq) was added followed by drop-wise addition of triethylamine (5.0 g, 3 eq). The mixture was stirred for 7 h after which time the reaction was quenched by 1N HCl to form a biphasic mixture. The layers were separated and the organic layer was washed with a saturated aqueous NaHCO3 solution. The organic layer was then concentrated under reduced pressure to provide pent-4-en-1-yl 2-(2-ethoxy-2-oxoacetamido)propanoate as a yellow oil. 1H NMR (400 MHz, CDCl3) δ ppm 7.64 (d, J=6.94 Hz, 1H), 5.66-5.83 (m, 1H), 4.90-5.05 (m, 2H), 4.49-4.62 (m, 1H), 4.31 (qd, J=7.17, 2.26 Hz, 2H), 4.13 (td, J=6.59, 2.13 Hz, 2H), 2.02-2.14 (m, 2H), 1.67-1.78 (m, 2H), 1.44 (d, J=7.19 Hz, 3H), 1.34 (t, J=7.15 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ ppm 171.64, 159.94, 155.83, 136.94, 115.40, 64.98, 63.10, 48.40, 29.71, 27.44, 17.88, 13.80; HRMS (M+Na) m/z, calcd for C12H19NO5Na, 280.1161; found, 280.1166. was added The mixture was stirred a further 18 h at ambient temperature at which was quenched with 1N HCl A biphasic mixture was formed the layers were separated The organic layer was washed with saturated aqueous NaHCO3 solution concentrated

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 pent-4-en-1-ol (0.62 g, 7.21 mmol) and DIPEA (1.26 mL, 7.21 mmol) in anhydrous 1,4-dioxane (20 ml), at 10° C. and under nitrogen, was slowly added a solution of triphosgene (0.75 g, 2.52 mmol) in anhydrous 1,4-dioxane (20 mL). The reaction mixture was stirred at RT for 1 hour, and ethyl (2S)-2-aminonon-8-enoate*HCl (0.85 g, 3.61 mmol) and 1 M aqueous NaOH (7.21 ml, 7.21 mmol) added, and the reaction mixture was heated to 50° C. for 15 hours. After cooling to RT, the reaction mixture was basified to pH 8 with 1M aqueous NaOH and extracted with ether (3×200 ml). The combined organic phases were washed with water (100 mL), brine (50 mL), dried over Na2SO4, filtered and concentrated. The residue was chromatographed on silica gel (5 to 75% EtOAc in hexane) to give the title compound (0.96 g). LRMS (ESI) m/z 312.5 [(M+H)+; calcd for C17H30NO4: 312.2]. the reaction mixture was heated to 50° C. for 15 hours After cooling to RT extracted with ether (3×200 ml) The combined organic phases were washed with water (100 mL), brine (50 mL) dried over Na2SO4 filtered concentrated The residue was chromatographed on silica gel (5 to 75% EtOAc in hexane)

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Diisopropylethyl amine (9.85 g, 76.2 mmol) was added dropwise to a 0° C. solution of 4-penten-1-ol (7.22 g, 83.9 mmol) and triphosgene (11.3 g, 38.1 mmol) in 160 mL dioxane. The resulting white suspension was stirred for 5 minutes at 0° C., then allowed to warm to 25° C. over 1 hour. The suspension was cooled to 0° C. with an ice bath and 1 N NaOH (76.2 mL) and L-t-butylglycine (10.0 g, 76.2 mmol) were added. The reaction mixture was warmed to 25° C. and stirred for 18 hours. The dioxane was removed in vacuo and the reaction mixture was basified to pH 12 with 1 N NaOH. The aqueous layer was extracted with DCM (3×150 mL), then acidified to pH˜1 with 6 N HCl. The aqueous layer was extracted with DCM (3×150 mL). The combined organic layers were dried over MgSO4 and concentrated to give the compound as a tan oil (13.7 g, 73.9% yield). LRMS (ESI) m/z 244 [(M+H)+; calcd for C12H22NO4 244]. to warm to 25° C. over 1 hour The suspension was cooled to 0° C. with an ice bath The reaction mixture was warmed to 25° C. stirred for 18 hours The dioxane was removed in vacuo The aqueous layer was extracted with DCM (3×150 mL) The aqueous layer was extracted with DCM (3×150 mL) The combined organic layers were dried over MgSO4 concentrated

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

实验步骤: Following the general procedure in Example 13A, 4-pentenol was added to butadiene monoepoxide, using the following quantities of reagents and solvents: Pd2dba3.CHCl3 (5.2 mg, 5.0 μmol), (S,S)-9 (11.8 mg, 15 μmol), DMAP (6.2 mg, 50 μmol), a 1.0 M solution of Et3B in THF (5.0 μL, 5.0 μmol), 4-pentenol (207 μL, 2.0 mmol), butadiene monoepoxide (81 μL, 1.0 mmol), CH2Cl2 (10 mL). The reaction time in this case was 4 h. Flash chromatography of the crude material (silica gel, 4:1 pentane-ether) afforded 131 mg (84%) of a colorless oil in 90% ee (separated by chiral GLC, Cyclosil B column, isothermal 120° C., (S)-(+)-isomerrt=9.33 min, (R)-(−)-isomerrt=9.68 min). [α]D=−33.2° (c 2.86, CHCl3); 1H NMR (300 MHz) δ 1.66 (quint 2H, J=7 Hz), 2.07-2.26 (m, 3H), 3.28-3.61 (m, 4H), 3.75-3.81 (m, 1H), 4.94 (d, 1H, J=11 Hz), 5.00 (d, 1H, J=17 Hz), 5.24 (d, 1H, J=9 Hz), 5.28 (d, 1H, J=17 Hz), 5.60-5.83 (m, 2H). 13C NMR (75.5 MHz) δ 28.9, 30.4, 65.2, 68.2, 81.6, 114.8, 118.7, 135.4, 138.2. Anal. Calc'd. for C9H16O2: C, 69.19; H, 10.32. Found: C, 69.23; H, 10.14.

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

实验步骤: To a solution of 4-penten-1-ol (640 mg, 7.5 mmol) and sodium hydride (260 mg, 7.5 mmol) in dry tetrahydrofuran was added a solution of 3-(4-chloro-1,2,5-thiadiazol-3-yl)pyridine (490 mg, 2.5 mmol) in dry tetrahydrofuran. The reaction mixture was stirred at room temperature for 1 h. Water was added and the mixture was extracted with ether. The ether phase was dried and evaporated to give the title compound. the mixture was extracted with ether The ether phase was dried evaporated

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

实验步骤: To a solution of 4-penten-1-ol (640 mg, 7.5 mmol) and sodium hydride (260 mg, 7.5 mmol) in dry tetrahydrofuran was added a solution of 3-(4-chloro-1,2,5-thiadiazol-3-yl)pyridine (490 mg, 2.5 mmol) in dry tetrahydrofuran. The reaction mixture was stirred at room temperature for 1 h. Water was added and the mixture was extracted with ether. The ether phase was dried and evaporated to give the title compound. the mixture was extracted with ether The ether phase was dried evaporated

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

实验步骤: To a solution of 4-penten-1-ol (640 mg, 7.5 mmol) and sodium hydride (260 mg, 7.5 mmol) in dry tetrahydrofuran was added a solution of 3-(4-chloro-1,2,5-thiadiazol-3-yl)pyridine (490 mg, 2.5 mmol) in dry tetrahydrofuran. The reaction mixture was stirred at room temperature for 1 h. Water was added and the mixture was extracted with ether. The ether phase was dried and evaporated to give the title compound. the mixture was extracted with ether The ether phase was dried evaporated

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

实验步骤: To a solution of 4-penten-1-ol (640 mg, 7.5 mmol) and sodium hydride (260 mg, 7.5 mmol) in dry tetrahydrofuran was added a solution of 3-(4-chloro-1,2,5-thiadiazol-3-yl)pyridine (490 mg, 2.5 mmol) in dry tetrahydrofuran. The reaction mixture was stirred at room temperature for 1 h. Water was added and the mixture was extracted with ether. The ether phase was dried and evaporated to give the title compound. the mixture was extracted with ether The ether phase was dried evaporated

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

实验步骤: To a suspension of 19.1 g of 50% sodium hydride under argon in 300 ml of N,N-dimethylformamide is added dropwise over a period of 1 hour, with stirring a solution of 37 g of 4-penten-1-ol, 2-methanol (prepared as described by B. K. Wasson, et. al., J. Chem. Soc., 39, 923 (1961)) in 200 ml of tetrahydrofuran. After stirring another 30 minutes, 126.34 g of hexadecyloxytosylate is added followed by 500 ml of tetrahydrofuran. This mixture is stirred for 2.5 hours, then heated to 80° C. for 20 minutes and then at room temperature overnight. Water is added and the mixture extracted with ether. The ether extract is dried and then evaporated. The residue is distilled using a Kugelrohr. The fraction distilling at 200°-210° C. 1 mm is collected, purified by chromatography and then redistilled, to give 11.35 g of the desired compound. is added dropwise over a period of 1 hour This mixture is stirred for 2.5 hours at room temperature overnight the mixture extracted with ether The ether extract is dried evaporated The residue is distilled The fraction distilling at 200°-210° C 1 mm is collected purified by chromatography redistilled

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

实验步骤: To a suspension of 19.1 g of 50% sodium hydride under argon in 300 ml of N,N-dimethylformamide is added dropwise over a period of 1 hour, with stirring a solution of 37 g of 4-penten-1-ol, 2-methanol (prepared as described by B. K. Wasson, et. al., J. Chem. Soc., 39, 923 (1961)) in 200 ml of tetrahydrofuran. After stirring another 30 minutes, 126.34 g of hexadecyloxytosylate is added followed by 500 ml of tetrahydrofuran. This mixture is stirred for 2.5 hours, then heated to 80° C. for 20 minutes and then at room temperature overnight. Water is added and the mixture extracted with ether. The ether extract is dried and then evaporated. The residue is distilled using a Kugelrohr. The fraction distilling at 200°-210° C. 1 mm is collected, purified by chromatography and then redistilled, to give 11.35 g of the desired compound. is added dropwise over a period of 1 hour This mixture is stirred for 2.5 hours at room temperature overnight the mixture extracted with ether The ether extract is dried evaporated The residue is distilled The fraction distilling at 200°-210° C 1 mm is collected purified by chromatography redistilled

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

实验步骤: 9-Borabicyclo[3.3.1]nonane (9-BBN) dissolved in 15 ml of tetrahydrofuran (manufactured by Aldrich Co.) was added to 300 mg (3.483 mmol) of 4-pentene-1-ol and allowed to react at 25° C. for 24 hours. Then, 4-bromopyridine hydrochloride (manufactured by Aldrich Co.) dissolved in water/dimethylformamide (DMF) at a ratio of 2:8, tetrakis(triphenylphosphine)palladium (manufactured by Aldrich Co.), and potassium carbonate (manufactured by Aldrich Co.) were added thereto in an equivalent ratio of 1:1.2:0.2 and allowed to react at 70° C. for 6 hours. Then, solvent was removed under reduced pressure, and the residual material was diluted with ethyl acetate and filtered with Celite. The material thus obtained was purified by column chromatography (column: silica (manufactured by Aldrich Co.), solvent: ethyl acetate/hexane) to obtain 203 mg of pyridinepentanol (yield rate: 48%). The reaction scheme is shown below. to react at 25° C. for 24 hours were added to react at 70° C. for 6 hours Then, solvent was removed under reduced pressure the residual material was diluted with ethyl acetate filtered with Celite The material thus obtained was purified by column chromatography (column: silica (manufactured by Aldrich Co.), solvent: ethyl acetate/hexane)