73% |
With caesium carbonate In N,N-dimethyl-formamide at 20℃; for 12h; |
223
Example 223; 3-(S)-(4-(3-Methyl-but-2-enyloxy)-benzyl)-piperazine-2,5-dione; To a suspension of 3- (S)- (4-hydroxy-benzyl)-piperazine-2, 5-dione (15 g, 68.2 mmol), cesium carbonate (111 g, 340 mmol), and tetrabutylammonium iodide (1.25 g, 3.4 mmol) in anhydrous DMF (500 mL), add at once, at ambient temperature, l-bromo-3- methyl-but-2-ene (51 g, 340 mmol). Stir 12 hours then add water (300 mL). Concentrate to dryness then add water (500 mL) and extract with a dichloromethane/isopropyl alcohol (3/1) mixture. Wash the organic phases with 10% aqueous potassium carbonate and water then dry over magnesium sulfate. Evaporate the solvent, then triturate the resulting solid with chloroform. Filter and dry to yield (14.3 g, 73%) of the title compound as a white solid: mp 217-220 °C :'H NMR (DMSO-d6): 8 1.69 (s, 3H), 1.74 (s, 3H), 2.84-2. 76 (m, 2H), 3.02 (dd, 1H), 3.36 (dd, 1H), 4.01 (m, 1H), 4.48 (d, 2H), 5.41 (m, 1H), 6.84 (d, 2H), 7.05 (d, 2H), 7.86 (s, 1H), 8.12 (d, 1H). |
46% |
With potassium carbonate In N,N-dimethyl-formamide at 20℃; |
2.2.7. Compound 3 (c[Tyr(O-Dal)-Gly])
DKP 2 (0.108 g, 0.5 mmol) was alkylated in DMF (5 mL),K2CO3 (0.339 mg) and 3,3-dimethylallyl-bromide (0.3 mL) byfollowing the general O-alkylation procedure described above.After the work-up the crude residue was treated with Et2O togive the pure product 3 in 46% of yield. Rf=0.2 (CHCl3/MeOH95:5). 1H NMR (DMSO-d6) δ: 1.66 and 1.71 (6H, 2d, 2 × CH3Dal); 2.65-3.02 (4H, m, βCH2 Tyr and CH2 Gly); 4.00 (2H, d, α-CH Tyr); 4.45 (2H, d, O-CH2 Dal); 5.39 (1H, t,_CHCH2O);6.81 and 7.15 (4H, 2d, aromatics); 7.87 and 8.11 (2H, br, NHTyrand NH Gly). |