反应详情

2-((tert-Butoxycarbonyl)amino)-2-methylpropanoic acid (Boc-Aib-OH, 54, 10.0 g, 49.2 mol), EDC.HCl (11.3 g, 59.0 mmol), HOBt (9.97 g, 73.8 mmol) and DIPEA (25.6 mL, 148 mmol) were stirred in 250 mL of THF until all solids dissolved. N-methyl-piperazine was added (10.9 mL, 98.4 mmol) and the reaction was stirred at room temperature for 18 hrs. The mixture was diluted with 300 mL of EtOAc and washed twice with saturated aqueous NaHCO3. The organic layer was then washed with brine, dried over MgSO4, filtered, and the solvent was removed in vacuo. This crude material was dissolved in 300 mL of CH3CN. HCl (4N in dioxane, 49 mL, 196 mmol) was added over 10 minutes. The reaction was stirred for 8 hrs, during which time the product forms a white precipitate. The product was filtered, washed with CH2Cl2, and dried under high vacuum over night to provide the product 55 as the bis-hydrochloride salt (10.4 g, 82% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.30 (br. s., 3 H), 4.35 (d, J=13.6 Hz, 2 H), 3.52 (br. s., 2 H), 3.41 (d, J=11.1 Hz, 2 H), 3.01 (q, J=11.1 Hz, 2 H), 2.77 (d, J=3.5 Hz, 3 H), 1.56 (s, 6 H). MS (ES+) [M+H]+=186.

1. dissolutiondissolved
2. washwashed twice with saturated aqueous NaHCO3
3. washThe organic layer was then washed with brine
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. customthe solvent was removed in vacuo
7. dissolutionThis crude material was dissolved in 300 mL of CH3CN
8. stirringThe reaction was stirred for 8 hrs, during which time the product forms a white precipitate
9. filtrationThe product was filtered
10. washwashed with CH2Cl2
11. customdried under high vacuum over night