Methyl N-((tert-butoxycarbonyl)glycyl)-N-methylglycinate

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

実験手順: Lithium hydroxide monohydrate (598 mg, 14.3 mmol) was added to a solution of 200 (1.22 g, 4.7 mmol) in 20 mL of THF—CH3OH—H2O (3:1:1) at 25° C. and the resulting reaction mixture was stirred for 3 h. The reaction mixture was poured onto 3M aqueous HCl (10 mL) and extracted with EtOAc (3×20 mL). The combined organic phases were dried (Na2SO4), filtered and concentrated in vacuo to give 300 (1.16 g, 1.16 g theoretical, 100%) as a colorless oil. This acid was identical to authentic material14 and was used directly in the next step without further purification: 1H NMR (CDCl3, 400 MHz)14 5.76 and 5.66 (two br s, 1H), 4.11, 4.00, and 3.91 (three s, 4H), 2.99 and 2.95 (two s, 3H), 1.38 (s, 9H); IR (neat)max 3348, 2979, 2937, 1717, 1654, 1691, 1409, 1368, 1287, 1252, 1167, 1053, 1030, 954, 866, 782, 736 cm−1. the resulting reaction mixture extracted with EtOAc (3×20 mL) The combined organic phases were dried (Na2SO4) filtered concentrated in vacuo

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

実験手順: Lithium hydroxide monohydrate (598 mg, 14.3 mmol) was added to a solution of 200 (1.22 g, 4.7 mmol) in 20 mL of THF—CH3OH—H2O (3:1:1) at 25° C. and the resulting reaction mixture was stirred for 3 h. The reaction mixture was poured onto 3M aqueous HCl (10 mL) and extracted with EtOAc (3×20 mL). The combined organic phases were dried (Na2SO4), filtered and concentrated in vacuo to give 300 (1.16 g, 1.16 g theoretical, 100%) as a colorless oil. This acid was identical to authentic material14 and was used directly in the next step without further purification: 1H NMR (CDCl3, 400 MHz)14 5.76 and 5.66 (two br s, 1H), 4.11, 4.00, and 3.91 (three s, 4H), 2.99 and 2.95 (two s, 3H), 1.38 (s, 9H); IR (neat)max 3348, 2979, 2937, 1717, 1654, 1691, 1409, 1368, 1287, 1252, 1167, 1053, 1030, 954, 866, 782, 736 cm−1. the resulting reaction mixture extracted with EtOAc (3×20 mL) The combined organic phases were dried (Na2SO4) filtered concentrated in vacuo

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of Boc-Gly-OH (2.70 g, 15.4 mmol) and the HCl salt of H2N-Sar-OMe (2.15 g, 15.4 mmol) in CH2Cl2 (50 mL) was treated sequentially with Et3N (2.2 mL, 15.8 mmol), DCC (3.20 g, 15.5 mmol), and DMAP (306 mg, 2.5 mmol) and the reaction mixture was stirred at 25° C. for 20 h. A white precipitate formed in the first 10 min and was removed by filtration at the end of the reaction. The filtrate was concentrated in vacuo. Flash chromatography (SiO2, 5×16 cm, 40% EtOAc-hexane eluent) afforded 200 (3.21 g, 4.01 g, theoretical, 80%) as a colorless oil which solidified on standing: mp 72-73° C. (EtOAc-hexane, colorless cubes); Rf=0.32 (50% EtOAc-hexane); 1H NMR (CDCl3, 400 MHz) 4:1 mixture of two conformers, for the major conformer: 5.44 (s, 1H), 4.14 (s, 2H), 4.02 (d, 2H, J=4.3 Hz), 3.73 (s, 3H), 3.02 (s, 3H), 1.43 (s, 9H); 13C NMR (CDCl3, 100 MHz) for major conformer: 169.3, 168.7, 155.7, 79.6, 52.2, 49.4, 42.2, 35.2, 28.3; IR (KBr)max 3419, 2978, 2934, 1754, 1715, 1667, 1488, 1424, 1367, 1249, 1208, 1175, 1120, 1051, 952, 871, 764, 712 cm−1; FABHRMS (NBA-NaI) m/z 283.1259 (M+Na+, C11H20N2O5 requires 283.1270). A white precipitate formed in the first 10 min was removed by filtration at the end of the reaction The filtrate was concentrated in vacuo

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of Boc-Gly-OH (2.70 g, 15.4 mmol) and the HCl salt of H2N-Sar-OMe (2.15 g, 15.4 mmol) in CH2Cl2 (50 mL) was treated sequentially with Et3N (2.2 mL, 15.8 mmol), DCC (3.20 g, 15.5 mmol), and DMAP (306 mg, 2.5 mmol) and the reaction mixture was stirred at 25° C. for 20 h. A white precipitate formed in the first 10 min and was removed by filtration at the end of the reaction. The filtrate was concentrated in vacuo. Flash chromatography (SiO2, 5×16 cm, 40% EtOAc-hexane eluent) afforded 200 (3.21 g, 4.01 g, theoretical, 80%) as a colorless oil which solidified on standing: mp 72-73° C. (EtOAc-hexane, colorless cubes); Rf=0.32 (50% EtOAc-hexane); 1H NMR (CDCl3, 400 MHz) 4:1 mixture of two conformers, for the major conformer: 5.44 (s, 1H), 4.14 (s, 2H), 4.02 (d, 2H, J=4.3 Hz), 3.73 (s, 3H), 3.02 (s, 3H), 1.43 (s, 9H); 13C NMR (CDCl3, 100 MHz) for major conformer: 169.3, 168.7, 155.7, 79.6, 52.2, 49.4, 42.2, 35.2, 28.3; IR (KBr)max 3419, 2978, 2934, 1754, 1715, 1667, 1488, 1424, 1367, 1249, 1208, 1175, 1120, 1051, 952, 871, 764, 712 cm−1; FABHRMS (NBA-NaI) m/z 283.1259 (M+Na+, C11H20N2O5 requires 283.1270). A white precipitate formed in the first 10 min was removed by filtration at the end of the reaction The filtrate was concentrated in vacuo