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Improved Access to Imidazole‐phosphonic Acids: Synthesis of D ‐ manno ‐Tetrahydroimidazopyridine‐2‐phosphonates
Author(s) -
Terinek Miroslav,
Vasella Andrea
Publication year - 2004
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.200490067
Subject(s) - chemistry , phosphonate , yield (engineering) , imidazole , alkylation , transesterification , stereochemistry , medicinal chemistry , organic chemistry , catalysis , materials science , metallurgy
The D ‐ manno ‐tetrahydroimidazopyridine‐2‐phosphonate 11 was prepared via a high‐yielding Pd(PPh 3 ) 4 ‐catalysed diphenylphosphonylation of the manno ‐iodoimidazole 12 , followed by transesterification to the diethyl phosphonate 14 and dealkylation, providing 11 in eight steps from the thionolactam 1 and in an overall yield of 15%. Alternatively, a more highly convergent synthesis based on the HgCl 2 /Et 3 N‐promoted condensation of the thionolactam 1 with the α ‐aminophosphonate 24 in THF led to 11 in four steps and in the same overall yield. In the presence of HgCl 2 /Et 3 N, the thionolactam 1 reacted at 80° with 2‐methoxyethanol to provide 66% of a 64 : 36 mixture of the gluco ‐ and manno ‐iminoethers 29 / 30 . Performing the reaction at 22° yielded preferentially the gluco ‐isomer 29 (86%, 84 : 16).