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OPPI BRIEFS

NEW SYNTHESES OF bis(TETRAMETHYLENE)FLUOROFORMAMIDINIUM HEXAFLUOROPHOSPHATE (BTFFH) AND 1,3-DIMETHYL-2-FLUORO-4,5-DIHYDRO-1H-IMIDAZOLIUM HEXAFLUOROPHOSPHATE (DFIH). UTILITY IN PEPTIDE COUPLING REACTIONS

Pages 477-481 | Received 05 Jun 1998, Published online: 09 Feb 2009

References

  • Carpino , L. A. and El-Faham , Ayman . 1995 . J. Am. Chem. Soc. , 117 : 5401
  • Vojkovsky , T. and Drake , B. 1997 . Org. Prep. Proced. Int. , 29 : 497
  • Boas , U. , Pedersen , B. and Christensen , B. C. 1998 . Synth. Commun. , 28 : 1223 It was possible to carry out this preparation with a solution of POCl3 or oxalyl chloride in methylene chloride in place of neat POCl3. For example, preparation of TCFH using POCl3: To a stirred solution of N, N, N',N'-tetramethylurea (11.6 g, 0.1 mol) in 200 mL of dry methylene chloride, POCl3 (16.9 g, 0.11 mol) was added at 20-25°. After the reaction mixture was refluxed for 3 h and cooled to 20-25°, aqueous 60% HPF6 (15 mL) was added dropwise over a period of 5-10 min while maintaining the temperature at 0° due to the highly exothermic reaction. After complete addition, the reaction mixture was stirred for 5 min, 50 mL of water was added and the organic layer was collected and dried over MgSO4. After filtration, the solution was concentrated in vacuo to approximately 1/3 the volume and anhydrous ether was added with vigorous stirring to promote precipitation of the salt as a white soild which was collected and dried under vacuum, yield 19.6 g (70%), mp. 93°, 1H NMR (CD3CN): δ 3.3 (s). The same reaction was also carried out with oxalyl chloride in place of POCl3, yield 20.9 g (75%). The same method involving POCl3 in dichloromethane was used for the preparation of BTCFH yield 69%, mp. 148-149°,7 1H NMR (CD3CN): δ 2.06 (m, 4, CH2), 3.88 (m, 4, CH2N)
  • Carpino , L. A. 1993 . J. Am. Chem. Soc. , 115 : 4397
  • Wenschuh , H. , Beyermann , M. , Haber , H. , Seydel , J. K. , Krause , E. , Bienert , M. , Carpino , L. A. , El-Faham , A. and Albericio , F. 1995 . J. Org. Chem. , 60 : 405
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  • Kiso , Y. , Fujiwara , Y. , Kimura , T. , Nishitani , A. and Akaji , A. 1992 . Int. J. Peptide Protein Res. , 40 : 308
  • Carpino , L. A. , Sadat-Aalaee , D. , Chao , H. G. and DeSelms , R. H. 1990 . J. Am. Chem. Soc. , 112 : 9651
  • Carpino , L. A. and El-Faham , A. 1994 . J. Org. Chem. , 59 : 695
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  • Carpino , L. A. , El-Faham , A. , Minor , C. A. and Albericio , F. 1994 . Chem. Commun. , 201

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