L-焦谷氨酸乙酯

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

实验步骤: A suspension of 30.0 g of L-pyroglutamic acid 133 (232 mmol) in 100 ml of anhydrous ethanol was slowly added with 20 ml of SOCl2 (274 mmol, 1.2 eq.) at 0° C. and subsequently stirred for 15 h, and the batch was thawed to room temperature to form a clear solution. For work-up, all volatile components were completely removed under vacuum, the remaining residue was subsequently taken up in 500 ml of ethyl acetate and successively stirred over K2CO3 and MgSO4, each time removing the drying agent by suction. Filtration over a small amount of silica gel and solvent removal under vacuum afforded 36.0 g (230 mmol, 99%) of ester 203 in the form of a slightly yellowish, viscous oil. was thawed to room temperature to form a clear solution For work-up, all volatile components were completely removed under vacuum successively stirred over K2CO3 and MgSO4 each time removing the drying agent by suction Filtration over a small amount of silica gel and solvent removal under vacuum

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

实验步骤: A suspension of 30.0 g of L-pyroglutamic acid 133 (232 mmol) in 100 ml of anhydrous ethanol was slowly added with 20 ml of SOCl2 (274 mmol, 1.2 eq.) at 0° C. and subsequently stirred for 15 h, and the batch was thawed to room temperature to form a clear solution. For work-up, all volatile components were completely removed under vacuum, the remaining residue was subsequently taken up in 500 ml of ethyl acetate and successively stirred over K2CO3 and MgSO4, each time removing the drying agent by suction. Filtration over a small amount of silica gel and solvent removal under vacuum afforded 36.0 g (230 mmol, 99%) of ester 203 in the form of a slightly yellowish, viscous oil. was thawed to room temperature to form a clear solution For work-up, all volatile components were completely removed under vacuum successively stirred over K2CO3 and MgSO4 each time removing the drying agent by suction Filtration over a small amount of silica gel and solvent removal under vacuum

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

实验步骤: A mixture of ethanol and glutamic acid was initially charged in a stirred vessel (A). The fraction of glutamic acid was 0.1% of the ethanol fraction. The mixture was conveyed continuously through the reactor (C) at a pressure of 72 bar by a suitable pump (B). The tubular reactor (C) was heated to a temperature of 260° C. by the heater (D). A carrier stream of pure ethanol from the reservoir (F) was heated to the same temperature using the preheater (G). At the mixing point (H), the carrier stream was mixed with the reactant stream (ratio 50/50) and fed to the reactor (C). The preheating temperature selected was so high that there was already reaction temperature at the mixing point, so that the temperature gradient in the reactor (C) was sufficiently small to prevent carbonization at the wall. The residence time in the tubular reactor (C) was 40 sec. With the aid of the control valve (E), the pressure was kept at the target value mentioned. At the outlet of the system, the reacted solution was introduced into 1 molar HCl. According to HPLC, 50% product yield (ethyl pyroglutamate) was obtained. reaction temperature at the mixing point

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Ethyl (2S)-5-oxopyrrolidine-2-carboxylate (0.200 g, 1.27 mmol) was azeotroped three times from toluene (25 mL each), dissolved in tetrahydrofuran (4.4 mL) and cooled to −78° C. 1 M lithium hexamethyldisilazide in tetrahydrofuran (1 M, 3.75 mL) was added via syringe and the colorless solution was stirred 30 min before addition of 2-[4-(bromomethyl)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.4 g, 1.0 mmol) in tetrahydrofuran (2.0 mL). The slightly yellow solution was stirred at −78° C. for 30 min and then at −10° C. for 1 h and warmed to rt for an additional 1 h before it was cooled back to −78° C. and quenched with acetic acid (1.00 mL, 17.6 mmol). Evaporation and purification by preparative LCMS gave the desired product as a colorless glass, (296 mg, 62%). 1H NMR (400 MHz, CD3OD): δ 7.67 (d, J=7.4 Hz, 2H), 7.22 (d, J=7.4 Hz, 2H), 4.20 (q, J=7.2 Hz, 2H), 3.08 (d, J=13.0 Hz, 1H), 3.05 (d, J=13.0 Hz, 1H), 2.35 (m, 1H), 2.23 (m, 1H), 2.15 (m, 1H), 1.79 (m, 1H), 1.35 (s, 12H), 1.25 (t, J=7.0 Hz, 3H); LCMS found for C20H29BNO5 (M+H)+: m/z=374. at −10° C. for 1 h warmed to rt for an additional 1 h before it was cooled back to −78° C. Evaporation and purification by preparative LCMS

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Ethyl (2S)-5-oxopyrrolidine-2-carboxylate (0.200 g, 1.27 mmol) was azeotroped three times from toluene (25 mL each), dissolved in tetrahydrofuran (4.4 mL) and cooled to −78° C. 1 M lithium hexamethyldisilazide in tetrahydrofuran (1 M, 3.75 mL) was added via syringe and the colorless solution was stirred 30 min before addition of 2-[4-(bromomethyl)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.4 g, 1.0 mmol) in tetrahydrofuran (2.0 mL). The slightly yellow solution was stirred at −78° C. for 30 min and then at −10° C. for 1 h and warmed to rt for an additional 1 h before it was cooled back to −78° C. and quenched with acetic acid (1.00 mL, 17.6 mmol). Evaporation and purification by preparative LCMS gave the desired product as a colorless glass, (296 mg, 62%). 1H NMR (400 MHz, CD3OD): δ 7.67 (d, J=7.4 Hz, 2H), 7.22 (d, J=7.4 Hz, 2H), 4.20 (q, J=7.2 Hz, 2H), 3.08 (d, J=13.0 Hz, 1H), 3.05 (d, J=13.0 Hz, 1H), 2.35 (m, 1H), 2.23 (m, 1H), 2.15 (m, 1H), 1.79 (m, 1H), 1.35 (s, 12H), 1.25 (t, J=7.0 Hz, 3H); LCMS found for C20H29BNO5 (M+H)+: m/z=374. at −10° C. for 1 h warmed to rt for an additional 1 h before it was cooled back to −78° C. Evaporation and purification by preparative LCMS

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

实验步骤: Ethyl (S)-(+)-2-pyrrolidone-5-carboxylate (1 g, 6.36 mmol) and benzyl bromide (0.76 mL, 6.36 mmol) were placed in dry THF (30 mL). The reaction mixture was stirred and cooled to 0° C. A 1M solution of tert-BuOK was added dropwise (6.36 ML, 6.36 mmol) and the reaction was stirred for an additional 0.5 h at 0° C. and allowed to come to room temperate where it was stirred for 24 hours under N2. The reaction was then dissolved into a 1:1 mixture of H2O/EtOAc. The organic layer was washed with 1M HCl, H2O and brine, and then dried over MgSO4 to afford N-benzyl-L-pyroglutamic acid ethyl ester an oil. the reaction was stirred for an additional 0.5 h at 0° C. was stirred for 24 hours under N2 The organic layer was washed with 1M HCl, H2O and brine dried over MgSO4

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

实验步骤: Ethyl (S)-(+)-2-pyrrolidone-5-carboxylate (1 g, 6.36 mmol) and benzyl bromide (0.76 mL, 6.36 mmol) were placed in dry THF (30 mL). The reaction mixture was stirred and cooled to 0° C. A 1M solution of tert-BuOK was added dropwise (6.36 ML, 6.36 mmol) and the reaction was stirred for an additional 0.5 h at 0° C. and allowed to come to room temperate where it was stirred for 24 hours under N2. The reaction was then dissolved into a 1:1 mixture of H2O/EtOAc. The organic layer was washed with 1M HCl, H2O and brine, and then dried over MgSO4 to afford N-benzyl-L-pyroglutamic acid ethyl ester an oil. the reaction was stirred for an additional 0.5 h at 0° C. was stirred for 24 hours under N2 The organic layer was washed with 1M HCl, H2O and brine dried over MgSO4

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

实验步骤: Ethyl (S)-(+)-2-pyrrolidone-5-carboxylate (1 g, 6.36 mmol) and benzyl bromide (0.76 mL, 6.36 mmol) were placed in dry THF (30 mL). The reaction mixture was stirred and cooled to 0° C. A 1M solultion of tert-BuOK was added dropwise (6.36 mL, 6.36 mmol) and the reaction was stirred for an additional 0.5 h at 0° C. and allowed to come to room temperate where it was stirred for 24 hours under N2. The reaction was then dissolved into a 1:1 mixture of H2O/EtOAc. The organic layer was washed with 1M HCl, H2O and brine, and then dried over MgSO4 to afford N-benzyl-L-pyroglutamic acid ethyl ester an oil. the reaction was stirred for an additional 0.5 h at 0° C. was stirred for 24 hours under N2 The organic layer was washed with 1M HCl, H2O and brine dried over MgSO4

反应条件: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Thionyl chloride (217 ml) is slowly added to a stirred suspension of L-glutamic acid (417 g) in dry ethanol (1 L), and the mixture is refluxed for 5 hours. Ethanol is removed under vaccum to give a residue, which is dissolved in water (500 ml). The water solution is made alkaline with saturated sodium carbonate solution and extracted with chloroform (4×200 ml). The chloroform extract is dried (Na2SO4) and evaporated to give crude product (178 g). This material is heated (160° C.) under vaccum (10 mm Hg) for 3 hours. Subsequent distillation gives pure ethyl L-pyroglutamate (126.6 g; b.p. 126° C./0.07 mm Hg; [α]D =-2.15°±0.01 (H2O, c=17.8). the mixture is refluxed for 5 hours Ethanol is removed under vaccum to give a residue, which extracted with chloroform (4×200 ml) The chloroform extract is dried (Na2SO4) evaporated to give crude product (178 g) Subsequent distillation

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

实验步骤: A suspension of 30.0 g of L-pyroglutamic acid 133 (232 mmol) in 100 ml of anhydrous ethanol was slowly added with 20 ml of SOCl2 (274 mmol, 1.2 eq.) at 0° C. and subsequently stirred for 15 h, and the batch was thawed to room temperature to form a clear solution. For work-up, all volatile components were completely removed under vacuum, the remaining residue was subsequently taken up in 500 ml of ethyl acetate and successively stirred over K2CO3 and MgSO4, each time removing the drying agent by suction. Filtration over a small amount of silica gel and solvent removal under vacuum afforded 36.0 g (230 mmol, 99%) of ester 203 in the form of a slightly yellowish, viscous oil. was thawed to room temperature to form a clear solution For work-up, all volatile components were completely removed under vacuum successively stirred over K2CO3 and MgSO4 each time removing the drying agent by suction Filtration over a small amount of silica gel and solvent removal under vacuum

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

实验步骤: A mixture of ethanol and glutamic acid was initially charged in a stirred vessel (A). The fraction of glutamic acid was 0.1% of the ethanol fraction. The mixture was conveyed continuously through the reactor (C) at a pressure of 72 bar by a suitable pump (B). The tubular reactor (C) was heated to a temperature of 260° C. by the heater (D). A carrier stream of pure ethanol from the reservoir (F) was heated to the same temperature using the preheater (G). At the mixing point (H), the carrier stream was mixed with the reactant stream (ratio 50/50) and fed to the reactor (C). The preheating temperature selected was so high that there was already reaction temperature at the mixing point, so that the temperature gradient in the reactor (C) was sufficiently small to prevent carbonization at the wall. The residence time in the tubular reactor (C) was 40 sec. With the aid of the control valve (E), the pressure was kept at the target value mentioned. At the outlet of the system, the reacted solution was introduced into 1 molar HCl. According to HPLC, 50% product yield (ethyl pyroglutamate) was obtained. reaction temperature at the mixing point

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Ethyl (2S)-5-oxopyrrolidine-2-carboxylate (0.200 g, 1.27 mmol) was azeotroped three times from toluene (25 mL each), dissolved in tetrahydrofuran (4.4 mL) and cooled to −78° C. 1 M lithium hexamethyldisilazide in tetrahydrofuran (1 M, 3.75 mL) was added via syringe and the colorless solution was stirred 30 min before addition of 2-[4-(bromomethyl)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.4 g, 1.0 mmol) in tetrahydrofuran (2.0 mL). The slightly yellow solution was stirred at −78° C. for 30 min and then at −10° C. for 1 h and warmed to rt for an additional 1 h before it was cooled back to −78° C. and quenched with acetic acid (1.00 mL, 17.6 mmol). Evaporation and purification by preparative LCMS gave the desired product as a colorless glass, (296 mg, 62%). 1H NMR (400 MHz, CD3OD): δ 7.67 (d, J=7.4 Hz, 2H), 7.22 (d, J=7.4 Hz, 2H), 4.20 (q, J=7.2 Hz, 2H), 3.08 (d, J=13.0 Hz, 1H), 3.05 (d, J=13.0 Hz, 1H), 2.35 (m, 1H), 2.23 (m, 1H), 2.15 (m, 1H), 1.79 (m, 1H), 1.35 (s, 12H), 1.25 (t, J=7.0 Hz, 3H); LCMS found for C20H29BNO5 (M+H)+: m/z=374. at −10° C. for 1 h warmed to rt for an additional 1 h before it was cooled back to −78° C. Evaporation and purification by preparative LCMS