反应详情

温度

5 °C

To a stirred suspension of 4-(tert-Butoxycarbonylamino)tetrahydro-2H-pyran-4-carboxylic acid, 20 g) in dimethylformamide was added (S)-2-amino-3-(4-iodophenyl)propanamide (Example 1, step (ii), 1.05 mol. eq.) and diisopropylethylamine (4 mol. eq.) at room temperature. The reaction mixture was cooled to 0-10° C. and stirred for 15 min. T3P (50% wt/wt in DMF; 1.7 mol. eq.) was added to the reaction mixture by dropwise addition at 0-10° C. over a period of 30 min and stirred for 1.5 h at the same temperature. The reaction mixture was quenched with water (2 rel. vol.) and stirred for 30 min at room temperature. 2-Methyltetrahydrofuran (15 rel. vol) and water (13 rel. vol) were added to the reaction mixture and extracted. The organic layer was separated and concentrated to 5 rel. vol. To the stirred organic portion was added toluene (10 rel. vol.) drop wise over a period of 30 min. The solution was stirred for 5 h at room temperature. The resulting solid material was filtered and washed with toluene (2 rel. vol), and dried the material at 50° C. under vacuum to afford the sub-titled compound (28.8 g).

1. stirringstirred for 1.5 h at the same temperature
2. customThe reaction mixture was quenched with water (2 rel. vol.)
3. stirringstirred for 30 min at room temperature
4. addition2-Methyltetrahydrofuran (15 rel. vol) and water (13 rel. vol) were added to the reaction mixture
5. extractionextracted
6. customThe organic layer was separated
7. concentrationconcentrated to 5 rel
8. additionvol. To the stirred organic portion was added toluene (10 rel
9. waitvol.) drop wise over a period of 30 min
10. stirringThe solution was stirred for 5 h at room temperature
11. filtrationThe resulting solid material was filtered
12. washwashed with toluene (2 rel. vol)
13. customdried the material at 50° C. under vacuum