¾µäºÏ³É·´Ó¦±ê×¼²Ù×÷¡ª°±»ùµÄ±£»¤¼°Íѱ£»¤ Ò©Ã÷¿µµÂÐÂÒ©¿ª·¢ÓÐÏÞ¹«Ë¾
immersed in an acetone¨Cdry ice bath, and a total of 300 mL of ammonia is passed through a drying tower containing potassium hydroxide pellets and collected in the flask. The bath is removed to permit the reaction to proceed at the boiling point of ammonia (?33¡æ), and a gentle stream of dry nitrogen is bubbled into the flask. A solution of 0.708 g (0.80250 mole) of N-benzyloxycarbonyl-L-methionine in 10 ml. of N,N-dimethylacetamide 1.02 g (1.40 ml., 0.0101 mole) of triethylamine and 1.25 g of freshly prepared palladium black are added. The nitrogen stream is discontinued and replaced by a stream of hydrogen that has been passed through a concentrated sulfuric acid scrubber. The mixture is stirred under reflux for 5.5 hours to effect hydrogenolysis. The hydrogen stream is discontinued, a flow of nitrogen is resumed, and the dry ice is removed from the reflux condenser, permitting rapid evaporation of ammonia. The flask is attached to a rotary evaporator, and the mixture is evaporated to dryness under reduced pressure. The residue is dissolved in water and filtered through a sintered funnel of medium porosity to remove the catalyst. The filtrate is evaporated to dryness, and the residue (354 mg, 95%) is crystallized from water¨Cethanol. The white crystalline product, after drying under reduced pressure at 25¡ã, weighs 272¨C305 mg. (73¨C82%), m.p. 280¨C282¡ã (dec.), [¦Á]25D +23.1¡ã (c = 1, aqueous 5 N hydrochloric acid).
Ëá½âÍѳý °±»ù¼×ËáÜÐõ¥ÔÚÇ¿ËáÐÔÌõ¼þÏÂÈÝÒ×È¥±£»¤¡£HBr/HOAc ÊÇËá½âÍѳýÜÐÑõôÊ»ùµÄ×î³£ÓõÄÊÔ¼Á[1]¡£Íѳý·´Ó¦Ö÷Òª°´ÏÂʽ½øÐÐ[2]¡£·´Ó¦ÐèÒªÏûºÄ2·Ö×ÓµÄHBr£¬CbzµÄÍѳýËÙ¶ÈËæHBrŨ¶ÈµÄÔö´ó¶øÔö´ó£¬Òò´Ëʵ¼ÊÉ϶¼ÊDzÉÓøßŨ¶ÈµÄ¹ýÁ¿HBr/HOAcÈÜÒº£¨1.2M-3.3M£©ÒÔ±£Ö¤·´Ó¦µÄÍêÈ«¡£
R2R1NCbz+R2H+R1NCbzH+Br-HBrCH2Br+CO2+H.HBrNR1R2
1. D. Ben-Ishai, A. Berger., J. Org. Chem., 1952, 17, 1564; R. A. Boissonnas, J. Blodinger, A. D. Welcher., J. Am. Chem. Soc., 1952, 74, 5309
2. R. A. Boissonnas, J. Blodinger, A. D. Welcher., J. Am. Chem. Soc., 1952, 74, 5309; J. Meienhofer, E. Schnabel., Z. Naturforsch., 1965, 20b, 661
º¬ÓÐË¿°±Ëá[1]ºÍËÕ°±Ëá[2]µÄëÄ»òÆäËüº¬ôÇ»ùµÄ°±»ùÑÜÉúÎïÓÃHBr/HOAcÍѳýCbzʱ»á·¢ÉúôÇ»ùµÄO-ÒÒõ£»¯·´Ó¦¡£ËäÈ»O-ÒÒõ£»ùÄÜÓüîÔí»¯»ò°±½âÍÑÈ¥£¬µ«ÎªÁ˱ÜÃâÕâ¸ö
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¸±·´Ó¦£¬¿ÉÒÔ¸ÄÓÃHBr/¶þÑõÁù»·»òHBr/Èý·úÒÒËáÀ´´úÌæHBr/HOAc[3]¡£ÓÉÓÚHBrÔÚÈý·úÒÒËáÖеÄÈܽâ¶È½ÏС£¬Òò´Ë²»ÄÜÔ¤ÏÈÖÆ³ÉHBr/Èý·úÒÒËáÈÜÒº£¬¶øÖ»Äܽ«±£»¤µÄëÄ»ò°±»ùÑÜÉúÎïÈÜÓÚÎÞË®Èý·úÒÒËáÖУ¬ÏÈÓÚ0¡æÏÂͨÈë¸ÉÔïµÄHBr£¬´ýCbz´ó²¿·ÖÍѳýºó£¬ÔÙÊÒÎÂͨ¶Ìʱ¼äÒÔÇóÍêÈ«Íѳý±ä»¯»ù¡£Cbz±»HBr·Ö½â²úÉúµÄä廯ÜÐÄÜͬëÄÖеÄijÖÖ°±»ùËá·´Ó¦£¬Ò²ÊÇÐèÒª¼ÓÒÔ×¢ÒâµÄ¡£È磬¼×Áò°±ËáµÄÁòÔ×ÓÄÜͬä廯Üз´Ó¦Éú³ÉS-Üлù¼×Áò°±Ëá[4]£¬·ÀÖ¹µÄ°ì·¨ÊǼÓÈëÁòÃÑ£¨CH3SC2H5£©Îª²¶×½¼Á[5]¡£É«°±Ëá±»HBr/HOAc·Ö½â²úÉúÓÐÉ«ÎïÖÊ£¬·ÀÖ¹µÄ°ì·¨ÊǼÓÈëÑÇÁ×Ëá¶þÒÒõ¥¡£Ïõ»ù¾«°±Ëá»á·¢ÉúÏõ»ùµÄ²¿·ÖÍÑÂ䣬¸ÄÓÃÒºÌåHBrÓÚ-67¡æ´¦Àí¿ÉÒÔ±ÜÃâ¡£
1. G. D. Fasman, E. R. Blout., J. Am. Chem. Soc., 1960, 82, 2262
2. S. Fujiwara, S. Moerinaga, K. Narita., Bull. Chem. Soc. Japan., 1962, 35, 438
3. J. Meienhofer, E. Schnabel., Z. Naturforsch., 1965, 20b, 661; »ÆÎ©µÂµÈ£¬ÉúÎﻯѧÓëÉúÎïÎïÀíѧ±¨, 1961, 98
4. N. F. Albertson, F. C. Mckay., J. Am. Chem. Soc., 1953, 73, 5323 5. S. Guttmann, R. A. Boissonnas, Helv. Chim. Acta., 1959, 42, 1257
ÓÃÒºÌåHFÔÚ0¡æ´¦Àí10-30·ÖÖÓ¼´¿É½«CbzÍêÈ«ÍÑÈ¥[1]¡£FSO3H[2]¡¢CH3SO3H[2, 3]¡¢CF3SO3H[3, 4]ºÍC6H5SCH3-TFA[5]Ò²ÊǽϺõÄÊÔ¼Á¡£Me3SiIÔÚÂȷ¡¢ÒÒëæÖÐÄÜÓÚ¼¸·ÖÖÓÄÚÑ¡ÔñÐÔÍÑÈ¥CbzºÍBoc±£»¤»ù[6]¡£¶ÔÓÚBBr3/CH2Cl2¶øÑÔ£¬½Ï´ó·Ö×ÓµÄëĵÄCbzÑÜÉúÎï¿ÉÔÚTFAÖÐÈ¥³ý£¬ÒòΪëÄÔÚËáÖеÄÈܽâ¶È±ÈÔÚCH2Cl2Öдó[7]¡£´ÓëÄÖÐÍÑÈ¥Cbz£¬¿ÉÔÚTFAÖÐÌí¼Ó0.5 M 4-£¨¼×Áò»ù£©±½·Ó[8]»òʹÓÃHF/Me2S/¶Ô¼×±½·Ó[9]£¨25:65:10,v/v£©À´ÒÖÖÆBn+¶Ô·¼Ïã°±»ùËáµÄ¼Ó³É¡£
1. S. Sakakibara et a1., Bull. Chem. Soc. Japan., 1967, 40, 2164; S. Matsuura, C. H. Niu, J. S. Cohen., J. Chem. Soc. Chem. Commun., 1976, 451
2. H. Yajima, H. Ogawa, H. Sakurai., J. Chem. Soc. Chem. Commun., 1977, 909 3. H. Yajima et a1., J. Chem. Soc. Chem. Commun., 1974, 107 4. H. Yajima et a1., Chem. Pharm. Bull., 1975, 23, 1164
5. Y. Kiso, K. Ukawa, T. Akita., J. Chem. Soc. Chem. Commun., 1980, 101
6. R. S.Lott, V. S. Chauham, C. H. Stammer., J. Chem. Soc. Chem. Commun., 1979, 495 7. J. Pless, W. Bauer., Angew Chem., Int. Ed. Engl., 1973, 12, 147; A. M. Felix., J. Org.
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Page 13 of 77
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Chem., 1974, 39, 1427
8. M. Bodanszky, A. Bodanszky., Int. J. Pept. Protein Res., 1984, 23, 287 9. J. P. Tam, W. F. Heath, R. B. Merrifield., J. Am. Chem. Soc., 1983, 105, 6442
´ËÍ⣬ÒѾ±¨µÀ¹ýµÄ»¹ÓÐÒÔϵÄһЩ²»³£Óõķ½·¨¡£ÈçHCl/CHCl3[1]¡¢HCl/HOAc[2]¡¢HBr/SO2[3]¡¢ÒºÌåHBr[4]¡¢TosOH[5]¡¢HI/HOAc[6]¡¢µâ»¯Á×[7]¡¢Et3SiH[8]¡¢·ÐÌÚµÄTFA[9]¡¢8M HClµÄÒÒ´¼Òº»ò6 M HCl»ØÁ÷1Сʱ[10]»òŨÑÎËáÓÚ25-75¡æ¼ÓÈÈ´¦Àí1-1.5Сʱ[11]µÈ¡£
1. G. D. Fasman, M. Idelson, E. R. Blout., J. Am. Chem. Soc., 1961, 83, 709 2. R. B. Merrifield., J. Am. Chem. Soc., 1963, 85, 2149 3. M. Idelson, E. R. Blout., J. Am. Chem. Soc., 1958, 80, 4631 4. M. Brenner, H. C. Curtius., Helv. Chim. Acta., 1963, 46, 2126 5. E. Taschner, B. Liberek, Abstr. Int. Cong. Biochemistry, Vienna 1958 6. E. Waldschmidt-Leitz, K. Kuhn., Chem. Ber., 1951, 84, 381
7. E. Brand, B. F. Erlanger, H. Sachs., J. Am. Chem. Soc., 1952, 74, 1849 8. Birkofer et al., Angew. Chem., Int. Ed., 1965, 4, 417 9. F. Weygand, W. Steglich., Z. Naturforsch., 1959, 14b, 472
10. A.E. Barkdoll, W. F. Ross., J. Am. Chem. Soc., 1944, 66, 567; G. Chelucci, M. Falorni, G. Giacomelli., Synthesis., 1990, 1121 11. J. White., J. Biol. Chem., 1934, 106, 141
2.1.2.8 HBr-AcOHÍѳýCbzʾÀý
OEtOOCNSNHNONHCbz33% HBrAcOH, 91%EtOOCNSNHONONH2.HBr
B. Anna; P. Gerald., Heterocycles, 2002, 58, 521
A solution of the amine Cbz compund (208 mg, 0.44 mmol) in 33 % hydrobromic acid in acetic acid (1 mL) and glacial acetic acid (0.6 mL) was stirred at rt for 3 h under an atmosphere of nitrogen. The volatiles were removed in vacuo to leave the free amine
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hydrobromide (168 mg, 91 %) as a brown, highly hygroscopic powder; [¦Á]D =-18.0¡ã (c = 0.4, EtOH);
2.1.2.9 TMSIÍѳýCbzʾÀý1
OOONH1BrONHCbzMe3SiIEt3N, CH3CNONH2BrONH2OO
US20040204397
Me3SiI (0.73 ml, 0.73 mmol) was added to a soluton of compound 1 (146 mg, 0.33 mmol) in acetonitrile (10 ml) at room temperature, and the resulting mixture was stirred at room temperature for 2 h. Et3N (0.12 ml) was added and the mixture was stirred at room temperature for 15 min. The solvents were removed in vacuo, and the residue was extracted with ethyl acetate. The combined organics were washed with sodium bicarbonate and brine, dried over sodium sulfate and filtered. Solvents were removed and the residue was used directly in the next step.
HNClNNH1NHCbzNNNMe3SiIEt3N, CH3CNClNNH2NH2HNNNN
US20050203078
2.1 g (4.45 mmol) of compound 1 in 30 ml of CH2Cl2 were combined with 1.9 ml (13.4 mmol) Me3SiI and stirred for 16 h at room temperature. Then 20 ml of MeOH were addede, the mixture was stirred for a further 30 min at room temperature and the reaction mixture was evaporated down completely. The residue was purified by chromatography on silica gel (eluding gradient: CH2Cl2/(MeOH/conc. Ammonia 95:5) = 70/30 ¨C 60/40) to yield compound 2 (690 mg, 56%).
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