methyl (2R,4R)-4-hydroxypyrrolidine-2-carboxylate

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Cis-4-Hydroxy-D-proline (15 g, 115 mmol) was suspended in 150 mL anhydrous methanol under an argon atmosphere, then cooled to 0° C. before bubbling in HCl gas for 15 minutes. The solution gradually became homogenous. The argon and HCl gas lines were removed and the solution was refluxed for 4 h. The solution was cooled and then concentrated under reduced pressure. The crude material was redissolved in 100 mL methanol and diethyl ether was added until a precipitate formed. The precipitate was filtered off, washed with diethyl ether, and dried in vacuo overnight to give 1 (20 g, 95%) as a white solid. MS: APCI (AP+): 146 (M)+. before bubbling in HCl gas for 15 minutes The argon and HCl gas lines were removed the solution was refluxed for 4 h The solution was cooled concentrated under reduced pressure The crude material was redissolved in 100 mL methanol diethyl ether was added until a precipitate formed The precipitate was filtered off washed with diethyl ether dried in vacuo overnight

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Cis-4-Hydroxy-D-proline (15 g, 115 mmol) was suspended in 150 mL anhydrous methanol under an argon atmosphere, then cooled to 0° C. before bubbling in HCl gas for 15 minutes. The solution gradually became homogenous. The argon and HCl gas lines were removed and the solution was refluxed for 4 h. The solution was cooled and then concentrated under reduced pressure. The crude material was redissolved in 100 mL methanol and diethyl ether was added until a precipitate formed. The precipitate was filtered off, washed with diethyl ether, and dried in vacuo overnight to reveal 1 (20 g, 95%) as a white solid. MS: APCI (AP+): 146 (M)+. before bubbling in HCl gas for 15 minutes The argon and HCl gas lines were removed the solution was refluxed for 4 h The solution was cooled concentrated under reduced pressure The crude material was redissolved in 100 mL methanol diethyl ether was added until a precipitate formed The precipitate was filtered off washed with diethyl ether dried in vacuo overnight

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 7.1 30 g of (2R,4R)-4-hydroxy pyrrolidine-2-carboxylic acid are suspended in 200 ml of methanol and cooled to 0° C. Thionyl chloride (18.1 ml) is subsequently added dropwise at the same temperature distributed over an hour. The reaction mixture (RM) is warmed to room temperature (RT) over 12 h, during which a clear solution forms. The solvent is removed in vacuo, and the residue obtained is recrystallised from ether, giving 50 g of methyl (2R,4R)-4-hydroxypyrrolidine-2-carboxylate; Rt.: 0.386 min; [M+H]+146.2. distributed over an hour The reaction mixture (RM) is warmed to room temperature (RT) over 12 h The solvent is removed in vacuo the residue obtained is recrystallised from ether

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a 250 ml round bottom flask equipped with a magnetic stir bar and a reflex condenser were placed dry methanol (40 ml) and cooled in ice bath under argon atmosphere. To this stirred solution was added acetyl chloride (4.32 g, 55 mmol) followed by cis-4-hydroxy-D-proline 34 (5.00 g, 38.17 mmol). The resulting solution was heated at reflex for 7-8 h and cooled to room temperature. The solution was diluted with ether, and the resulting white solid was collected by suction, was with ether and dried under vacuum over solid NaOH. Yield; 6.9 g (100%) . 1HNMR (CDCl3): 2.09 (2 dd, 1H), 2.34 (m, 1H), 3.49-3.73 (m, 3H), 3.79 (s, 3H, CH3), 4.34 (m, 2H) In a 250 ml round bottom flask equipped with a magnetic stir bar and a reflex condenser cooled in ice bath under argon atmosphere The resulting solution was heated at reflex for 7-8 h the resulting white solid was collected by suction dried under vacuum over solid NaOH

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Into a solution of 1 (10 g, 55 mmol) in anhydrous CHCl3 (100 mL) was added triethylamine (19 mL, 138 mmol) and triphenylmethyl chloride (14.5 g, 52 mmol). The mixture was stirred at RT for 3d before concentrating and redissolving in EtOAc. The solution was washed sequentially with 10% aq. citric acid, water, and brine before drying over MgSO4 and concentrating under reduced pressure to give 2 (20 g, 100%) as a yellow solid. before concentrating redissolving in EtOAc The solution was washed sequentially with 10% aq. citric acid, water, and brine before drying over MgSO4 concentrating under reduced pressure

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Cis-4-Hydroxy-D-proline (15 g, 115 mmol) was suspended in 150 mL anhydrous methanol under an argon atmosphere, then cooled to 0° C. before bubbling in HCl gas for 15 minutes. The solution gradually became homogenous. The argon and HCl gas lines were removed and the solution was refluxed for 4 h. The solution was cooled and then concentrated under reduced pressure. The crude material was redissolved in 100 mL methanol and diethyl ether was added until a precipitate formed. The precipitate was filtered off, washed with diethyl ether, and dried in vacuo overnight to give 1 (20 g, 95%) as a white solid. MS: APCI (AP+): 146 (M)+. before bubbling in HCl gas for 15 minutes The argon and HCl gas lines were removed the solution was refluxed for 4 h The solution was cooled concentrated under reduced pressure The crude material was redissolved in 100 mL methanol diethyl ether was added until a precipitate formed The precipitate was filtered off washed with diethyl ether dried in vacuo overnight

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Cis-4-Hydroxy-D-proline (15 g, 115 mmol) was suspended in 150 mL anhydrous methanol under an argon atmosphere, then cooled to 0° C. before bubbling in HCl gas for 15 minutes. The solution gradually became homogenous. The argon and HCl gas lines were removed and the solution was refluxed for 4 h. The solution was cooled and then concentrated under reduced pressure. The crude material was redissolved in 100 mL methanol and diethyl ether was added until a precipitate formed. The precipitate was filtered off, washed with diethyl ether, and dried in vacuo overnight to reveal 1 (20 g, 95%) as a white solid. MS: APCI (AP+): 146 (M)+. before bubbling in HCl gas for 15 minutes The argon and HCl gas lines were removed the solution was refluxed for 4 h The solution was cooled concentrated under reduced pressure The crude material was redissolved in 100 mL methanol diethyl ether was added until a precipitate formed The precipitate was filtered off washed with diethyl ether dried in vacuo overnight

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Into a solution of 1 (10 g, 55 mmol) in anhydrous CHCl3 (100 mL) was added triethylamine (19 mL, 138 mmol) and triphenylmethyl chloride (14.5 g, 52 mmol). The mixture was stirred at RT for 3d before concentrating and redissolving in EtOAc. The solution was washed sequentially with 10% aq. citric acid, water, and brine before drying over MgSO4 and concentrating under reduced pressure to give 2 (20 g, 100%) as a yellow solid. before concentrating redissolving in EtOAc The solution was washed sequentially with 10% aq. citric acid, water, and brine before drying over MgSO4 concentrating under reduced pressure

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Cis-4-Hydroxy-D-proline (15 g, 115 mmol) was suspended in 150 mL anhydrous methanol under an argon atmosphere, then cooled to 0° C. before bubbling in HCl gas for 15 minutes. The solution gradually became homogenous. The argon and HCl gas lines were removed and the solution was refluxed for 4 h. The solution was cooled and then concentrated under reduced pressure. The crude material was redissolved in 100 mL methanol and diethyl ether was added until a precipitate formed. The precipitate was filtered off, washed with diethyl ether, and dried in vacuo overnight to give 1 (20 g, 95%) as a white solid. MS: APCI (AP+): 146 (M)+. before bubbling in HCl gas for 15 minutes The argon and HCl gas lines were removed the solution was refluxed for 4 h The solution was cooled concentrated under reduced pressure The crude material was redissolved in 100 mL methanol diethyl ether was added until a precipitate formed The precipitate was filtered off washed with diethyl ether dried in vacuo overnight

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Into a solution of 1 (10 g, 55 mmol) in anhydrous CHCl3 (100 mL) was added triethylamine (19 mL, 138 mmol) and triphenylmethyl chloride (14.5 g, 52 mmol). The mixture was stirred at RT for 3d before concentrating and redissolving in EtOAc. The solution was washed sequentially with 10% aq. citric acid, water, and brine before drying over MgSO4 and concentrating under reduced pressure to give 2 (20 g, 100%) as a yellow solid. before concentrating redissolving in EtOAc The solution was washed sequentially with 10% aq. citric acid, water, and brine before drying over MgSO4 concentrating under reduced pressure

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Cis-4-Hydroxy-D-proline (15 g, 115 mmol) was suspended in 150 mL anhydrous methanol under an argon atmosphere, then cooled to 0° C. before bubbling in HCl gas for 15 minutes. The solution gradually became homogenous. The argon and HCl gas lines were removed and the solution was refluxed for 4 h. The solution was cooled and then concentrated under reduced pressure. The crude material was redissolved in 100 mL methanol and diethyl ether was added until a precipitate formed. The precipitate was filtered off, washed with diethyl ether, and dried in vacuo overnight to reveal 1 (20 g, 95%) as a white solid. MS: APCI (AP+): 146 (M)+. before bubbling in HCl gas for 15 minutes The argon and HCl gas lines were removed the solution was refluxed for 4 h The solution was cooled concentrated under reduced pressure The crude material was redissolved in 100 mL methanol diethyl ether was added until a precipitate formed The precipitate was filtered off washed with diethyl ether dried in vacuo overnight

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Cis-4-Hydroxy-D-proline (15 g, 115 mmol) was suspended in 150 mL anhydrous methanol under an argon atmosphere, then cooled to 0° C. before bubbling in HCl gas for 15 minutes. The solution gradually became homogenous. The argon and HCl gas lines were removed and the solution was refluxed for 4 h. The solution was cooled and then concentrated under reduced pressure. The crude material was redissolved in 100 mL methanol and diethyl ether was added until a precipitate formed. The precipitate was filtered off, washed with diethyl ether, and dried in vacuo overnight to reveal 1 (20 g, 95%) as a white solid. MS: APCI (AP+): 146 (M)+. before bubbling in HCl gas for 15 minutes The argon and HCl gas lines were removed the solution was refluxed for 4 h The solution was cooled concentrated under reduced pressure The crude material was redissolved in 100 mL methanol diethyl ether was added until a precipitate formed The precipitate was filtered off washed with diethyl ether dried in vacuo overnight