(E)-4-[[(1,1-DiMethylethyl)diMethylsilyl]oxy]-2-butenoic Acid Ethyl Ester

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

实验步骤: Ethyl 3-aminopropanoate HCl salt (4.6 g, 39.2 mmol, 1.4 eq) was added to a solution of (E)-ethyl 4-(tert-butyldimethylsilyloxy)but-2-enoate in 50 mL of ethanol. The mixture was stirred at RT overnight and then heated to reflux overnight. Another 9.2 g of 3-aminopropanoate HCl salt was added. The reaction was continued to heat at reflux for 2 hr. Solvents were removed; the yellow oily residue was dissolved in DCM, filtered through a pad of SiO2 (˜80 g), and washed with 800 mL EtOAc. The filtrate was concentrated to give the product 7.8 g (76%) as a light yellow liquid. HPLC retention time: T=1.844 min (analytical-3); ESI-MS:m/z 362.3 (M+H)+. heated to reflux overnight to heat at reflux for 2 hr Solvents were removed the yellow oily residue was dissolved in DCM filtered through a pad of SiO2 (˜80 g) washed with 800 mL EtOAc The filtrate was concentrated

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

实验步骤: Ethyl 3-aminopropanoate HCl salt (4.6 g, 39.2 mmol, 1.4 eq) was added to a solution of (E)-ethyl 4-(tert-butyldimethylsilyloxy)but-2-enoate in 50 mL of ethanol. The mixture was stirred at RT overnight and then heated to reflux overnight. Another 9.2 g of 3-aminopropanoate HCl salt was added. The reaction was continued to heat at reflux for 2 hr. Solvents were removed; the yellow oily residue was dissolved in DCM, filtered through a pad of SiO2 (˜80 g), and washed with 800 mL EtOAc. The filtrate was concentrated to give the product 7.8 g (76%) as a light yellow liquid. HPLC retention time: T=1.844 min (analytical-3); ESI-MS:m/z 362.3 (M+H)+. heated to reflux overnight to heat at reflux for 2 hr Solvents were removed the yellow oily residue was dissolved in DCM filtered through a pad of SiO2 (˜80 g) washed with 800 mL EtOAc The filtrate was concentrated

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

实验步骤: 2-(Tert-butyldimethylsilyloxy)acetaldehyde (10.0 g, 57.3 mmol) was added to a solution of (2-ethoxy-2-oxoethyl)triphenylphosphorane (20.0 g, 57.4 mmol) in 150 mL toluene, the mixture was stirred at RT overnight and then heated to 50° C. for 5 hrs. Solvents were removed and the residue was suspended in 400 mL of hexane. The solution was filtered, the filtrate was concentrated to give the product 3A as a colorless liquid 13.7 g (98%). 1H NMR (400 MHz, CDCl3) δ ppm 0.08 (s, 6H), 0.92 (s, 9H), 1.30 (t, 3H, 6 Hz), 4.21 (q, 2H, 6 Hz), 4.34 (dt, 2H), 6.09 (dt, 1H), 7.00 (dt, 1H); ESI-MS:m/z 245.3 (M+H)+, HPLC retention time: T=2.737 min (analytical-3). heated to 50° C. for 5 hrs Solvents were removed The solution was filtered the filtrate was concentrated

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

实验步骤: To a solution of ethyl (2E)-4-{[tert-butyl(dimethyl)silyl]oxy}but-2-enoate (3.27 g, 13.4 mmol) and N-benzyl-1-methoxy-N-((trimethylsilyl)methyl)methanamine (4.14 g, 17.5 mmol) in CH2Cl2 (30 mL) was added TFA (0.280 mL, 3.64 mmol) at 0° C. The reaction was stirred at rt overnight. The mixture was quenched with water (50 mL) and extracted with EtOAc (two×50 mL). The combined organic layers were dried over MgSO4 and concentrated. The residue was purified via flash chromatography eluting with 20% EtOAc/heptane to give the title compound as a pale yellow oil (2.61 g, 53 yield). 1H NMR (400 MHz, chloroform-d) δ ppm 7.08-7.41 (m, 5H), 4.10 (q, J=7.13 Hz, 2H), 3.42-3.73 (m, 4H), 2.37-2.90 (m, 6H), 1.22 (t, J=7.05 Hz, 3H), 0.84 (s, 9H), 0.00 (d, J=1.26 Hz, 6H). The mixture was quenched with water (50 mL) extracted with EtOAc (two×50 mL) The combined organic layers were dried over MgSO4 concentrated The residue was purified via flash chromatography eluting with 20% EtOAc/heptane

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

实验步骤: DIEA (2.75 mL, 16.6 mmol) and LiCl (5.54 g, 129 mmol) were added to a solution of tert-butyldimethylsilyloxy acetaldehyde (3.22 g, 18.5 mmol) and diethylmethylphosphonoacetate (4.66 g, 22.2 mmol) in CH3CN (40 mL) and the mixture was stirred at rt for 24 hrs. The mixture was quenched with water (50 mL) and extracted with EtOAc (50 mL). The organic layer was dried over MgSO4 and concentrated. The residue was purified via flash chromatography eluting with 25% EtOAc/heptane to give the title compound as a colorless oil (3.27 g, 72% yield). 1H NMR (400 MHz, chloroform-d) δ ppm 6.91 (dt, J=15.42, 3.49 Hz, 1H) 6.01 (dt, J=15.61, 2.27 Hz, 1H) 4.25 (dd, J=3.27, 2.27 Hz, 2H) 4.12 (q, J=7.22 Hz, 2H) 1.21 (t, J=7.18 Hz, 3H) 0.84 (s, 9H) 0.00 (s, 6H). The mixture was quenched with water (50 mL) extracted with EtOAc (50 mL) The organic layer was dried over MgSO4 concentrated The residue was purified via flash chromatography eluting with 25% EtOAc/heptane

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

实验步骤: DIEA (2.75 mL, 16.6 mmol) and LiCl (5.54 g, 129 mmol) were added to a solution of tert-butyldimethylsilyloxy acetaldehyde (3.22 g, 18.5 mmol) and diethylmethylphosphonoacetate (4.66 g, 22.2 mmol) in CH3CN (40 mL) and the mixture was stirred at rt for 24 hrs. The mixture was quenched with water (50 mL) and extracted with EtOAc (50 mL). The organic layer was dried over MgSO4 and concentrated. The residue was purified via flash chromatography eluting with 25% EtOAc/heptane to give the title compound as a colorless oil (3.27 g, 72% yield). 1H NMR (400 MHz, chloroform-d) δ ppm 6.91 (dt, J=15.42, 3.49 Hz, 1H) 6.01 (dt, J=15.61, 2.27 Hz, 1H) 4.25 (dd, J=3.27, 2.27 Hz, 2H) 4.12 (q, J=7.22 Hz, 2H) 1.21 (t, J=7.18 Hz, 3H) 0.84 (s, 9H) 0.00 (s, 6H). The mixture was quenched with water (50 mL) extracted with EtOAc (50 mL) The organic layer was dried over MgSO4 concentrated The residue was purified via flash chromatography eluting with 25% EtOAc/heptane

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

实验步骤: Ethyl 3-aminopropanoate HCl salt (4.6 g, 39.2 mmol, 1.4 eq) was added to a solution of (E)-ethyl 4-(tert-butyldimethylsilyloxy)but-2-enoate in 50 mL of ethanol. The mixture was stirred at RT overnight and then heated to reflux overnight. Another 9.2 g of 3-aminopropanoate HCl salt was added. The reaction was continued to heat at reflux for 2 hr. Solvents were removed; the yellow oily residue was dissolved in DCM, filtered through a pad of SiO2 (˜80 g), and washed with 800 mL EtOAc. The filtrate was concentrated to give the product 7.8 g (76%) as a light yellow liquid. HPLC retention time: T=1.844 min (analytical-3); ESI-MS:m/z 362.3 (M+H)+. heated to reflux overnight to heat at reflux for 2 hr Solvents were removed the yellow oily residue was dissolved in DCM filtered through a pad of SiO2 (˜80 g) washed with 800 mL EtOAc The filtrate was concentrated

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

实验步骤: 2-(Tert-butyldimethylsilyloxy)acetaldehyde (10.0 g, 57.3 mmol) was added to a solution of (2-ethoxy-2-oxoethyl)triphenylphosphorane (20.0 g, 57.4 mmol) in 150 mL toluene, the mixture was stirred at RT overnight and then heated to 50° C. for 5 hrs. Solvents were removed and the residue was suspended in 400 mL of hexane. The solution was filtered, the filtrate was concentrated to give the product 3A as a colorless liquid 13.7 g (98%). 1H NMR (400 MHz, CDCl3) δ ppm 0.08 (s, 6H), 0.92 (s, 9H), 1.30 (t, 3H, 6 Hz), 4.21 (q, 2H, 6 Hz), 4.34 (dt, 2H), 6.09 (dt, 1H), 7.00 (dt, 1H); ESI-MS:m/z 245.3 (M+H)+, HPLC retention time: T=2.737 min (analytical-3). heated to 50° C. for 5 hrs Solvents were removed The solution was filtered the filtrate was concentrated

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

实验步骤: To a solution of ethyl (2E)-4-{[tert-butyl(dimethyl)silyl]oxy}but-2-enoate (3.27 g, 13.4 mmol) and N-benzyl-1-methoxy-N-((trimethylsilyl)methyl)methanamine (4.14 g, 17.5 mmol) in CH2Cl2 (30 mL) was added TFA (0.280 mL, 3.64 mmol) at 0° C. The reaction was stirred at rt overnight. The mixture was quenched with water (50 mL) and extracted with EtOAc (two×50 mL). The combined organic layers were dried over MgSO4 and concentrated. The residue was purified via flash chromatography eluting with 20% EtOAc/heptane to give the title compound as a pale yellow oil (2.61 g, 53 yield). 1H NMR (400 MHz, chloroform-d) δ ppm 7.08-7.41 (m, 5H), 4.10 (q, J=7.13 Hz, 2H), 3.42-3.73 (m, 4H), 2.37-2.90 (m, 6H), 1.22 (t, J=7.05 Hz, 3H), 0.84 (s, 9H), 0.00 (d, J=1.26 Hz, 6H). The mixture was quenched with water (50 mL) extracted with EtOAc (two×50 mL) The combined organic layers were dried over MgSO4 concentrated The residue was purified via flash chromatography eluting with 20% EtOAc/heptane

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

实验步骤: DIEA (2.75 mL, 16.6 mmol) and LiCl (5.54 g, 129 mmol) were added to a solution of tert-butyldimethylsilyloxy acetaldehyde (3.22 g, 18.5 mmol) and diethylmethylphosphonoacetate (4.66 g, 22.2 mmol) in CH3CN (40 mL) and the mixture was stirred at rt for 24 hrs. The mixture was quenched with water (50 mL) and extracted with EtOAc (50 mL). The organic layer was dried over MgSO4 and concentrated. The residue was purified via flash chromatography eluting with 25% EtOAc/heptane to give the title compound as a colorless oil (3.27 g, 72% yield). 1H NMR (400 MHz, chloroform-d) δ ppm 6.91 (dt, J=15.42, 3.49 Hz, 1H) 6.01 (dt, J=15.61, 2.27 Hz, 1H) 4.25 (dd, J=3.27, 2.27 Hz, 2H) 4.12 (q, J=7.22 Hz, 2H) 1.21 (t, J=7.18 Hz, 3H) 0.84 (s, 9H) 0.00 (s, 6H). The mixture was quenched with water (50 mL) extracted with EtOAc (50 mL) The organic layer was dried over MgSO4 concentrated The residue was purified via flash chromatography eluting with 25% EtOAc/heptane