反应详情

温度

0 °C

To (S)-tert-butyl 1-(9H-fluoren-9-yl)-24,24-dimethyl-3,8,22-trioxo-2,12,15,18,23-pentaoxa-4,9,21-triazapentacosane-5-carboxylate (1.18 g, 1.69 mmol), in 1,4-dioxane (45 mL) chilled to 0° C. concentrated ammonia hydroxide (9.5 mL, 133 mmol) was added dropwise over 15 minutes. The reaction was stirred at 0° C. for 2 hours and then at ambient temperature for 16 hours. After this time, the reaction was dry loaded onto silica and purified by silica gel column chromatography eluting with methylene chloride to 3:17 methanol/methylene chloride to afford (S)-tert-butyl 21-amino-2,2-dimethyl-4,18-dioxo-3,8,11,14-tetraoxa-5,17-diazadocosan-22-oate (802 mg, 99%) as an off-white solid: 1H NMR (300 MHz, CDCl3) δ 6.92 (bs, 1H), 5.14 (bs, 3H), 3.90-3.85 (m, 1H), 3.80-3.54 (m, 9H), 3.49-3.45 (m, 2H), 3.34-3.29 (m, 2H), 3.23-3.15 (m, 3H), 2.61-2.41 (m, 2H), 2.33-2.23 (m, 1H), 2.15-2.03 (m, 1H), 1.48 (s, 9H), 1.46 (s, 9H); ESI MS m/z=478 [M+H]+.

1. additionwas added dropwise over 15 minutes
2. waitat ambient temperature for 16 hours
3. customAfter this time, the reaction was dry
4. custompurified by silica gel column chromatography
5. washeluting with methylene chloride to 3:17 methanol/methylene chloride