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With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0℃; for 1.5h; |
Di-Boc Phidianidine A (10):
General procedure: To a cooled (0 °C) suspension of 6-bromoindole-3-aceticacid (4) ADDIN EN.CITEBaran2006555517Baran,P. S.Shenvi, R.A.TotalSynthesis of (±)-Chartelline CJ. Am. Chem.Soc.J.Am. Chem.Soc.14028-140291282006Rasmussen199366617Rasmussen,T.Jensen, J.Anthoni,U.Christophersen,C.Nielsen, P.H.Structure and Synthesis of Bromoindoles from theMarine Sponge PseudosuberitesHyalinusJ. Nat.Prod.J.Nat. Prod.1553-15585619935 (0.231 g, 0.910mmol, 1.00 equiv) in 5 mL of CH2Cl2 was added a catalyticamount of anhydrous DMF (2 drops from a 50 mLsyringe), followed by oxalyl chloride (0.231 mL, 2.73 mmol, 3.00 equiv)dropwise by syringe. After stirring at 0 °C for 1.5 h, the reaction mixture wasconcentrated in vacuo to provide acidchloride 8 as a brown oil that wasused immediately. To a cooled (0 °C) solutionof N-hydroxyguanidine 3(0.403 g, 1.00 mmol, 1.10 equiv) in 5 mL of CH2Cl2 wasadded Et3N (0.380 mL, 2.73 mmol, 3.00 equiv). Then, a solution of crudeacid chloride 8 (0.176 g, 0.910mmol, 1.00 equiv) in 2 mL of CH2Cl2 was added dropwise bysyringe over 5 min. An additional 2 mL of CH2Cl2 was usedto rinse the flask containing the acid chloride, and this liquid was added tothe reaction flask. The cooling bath was removed, and the resulting orangesolution was allowed to warm to ambient temperature. After stirring at ambienttemperature for 3 h, the reaction mixture was concentrated in vacuo to provide a foamy orange-brown colored solid, which wasredissolved in 10 mL of 1,2-dichloroethane and heated at reflux for 2 h. Theresulting dark-brown colored solution was then concentrated in vacuo, partitioned between 7 mL ofsaturated aqueous NaHCO3 and 7 mL of CH2Cl2,and then the layers were separated. The aqueous layer was extracted with 4 8 mL of CH2Cl2, andthe combined organic extracts were dried over anhydrous Na2SO4,filtered, and concentrated in vacuoto afford a foamy orange-brown colored solid (0.589 g, 104% of theoretical).This solid was adsorbed onto 3 g of silica gel using EtOAc and then purified byflash column chromatography on silica gel (2:3 EtOAc/hexanes) to afford theproduct as a yellow-orange colored film (0.081 g, 14%). Spectral data for theproduct matches previously reported spectra for compound 14a prepared by Lin and Snider:ADDIN EN.CITELin2012464417Lin,H. -Y.Snider, B.B.Synthesisof Phidianidines A and BJ. Org.Chem.J.Org. Chem.4832-48367720126 Rf= 0.42 (5 elutions), 2:3 EtOAc/hexanes, visualized with UV and PMA/heat; 1HNMR (CDCl3, 400 MHz) d 11.49(br s, 1H), 8.43 (br s, 1H), 8.30 (br t, J= 4.8, 1H), 7.52 (s, 1H), 7.47 (d, J= 8.4, 1H), 7.23 (dd, J = 8.4, 1.2,1H), 7.17 (s, 1H), 4.34 (t, J = 5.6,1H), 4.18 (s, 2H), 3.35 (td, J = 7.2,5.6, 2H), 3.20 (dt, J = 6.8, 6.4,2H), 1.59-1.54 (m, 4H), 1.49 (s, 18H), 1.38-1.32 (m, 2H); 13C NMR(CDCl3, 100 MHz) d 176.9,168.8, 163.6, 156.2, 153.3, 137.0, 125.7, 123.7, 123.2, 120.0, 116.1, 114.3,108.4, 83.2, 79.4, 43.2, 40.7, 29.1, 28.7, 28.3, 28.1, 24.1, 23.3; IR (neat)3329, 2978, 2933, 2863, 1720, 1635, 1604, 1394, 1367, 1135, 1054, 733 cm-1;HRMS (TOF MS ES+) m / z calcd for C27H3879BrN7O5Na(M + Na)+ 642.2015, found 642.2024. |
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