合成路线1

Oxidation of cyclobutanemethanol (XXVIII) with NaOCl and catalytic TEMPO by means of KBr and NaHCO3 in CH2Cl2/H2O gives cyclobutanecarboxaldehyde (XXIX), which is then condensed with nitromethane in the presence of Et3N in toluene to yield the nitro alcohol (XXX). Subsequent treatment of alcohol (XXX) with acetic anhydride in the presence of DMAP furnishes a mixture of the acetate ester (XXXI) and the dehydration compound (2-nitrovinyl)cyclobutane (XXXII), which can also be obtained as the only reaction product by dehydration of nitro alcohol (XXX) with MsCl in the presence of Et3N. Reduction of the mixture of compounds (XXXI) and (XXXII) or the nitro olefin (XXXII) by catalytic hydrogenation over Pd/C in MeOH optionally in the presence of Et3N, or with NaBH4 in PEG-400/H2O or t-BuOH, affords (2-nitroethyl)cyclobutane (XXXIII), which is condensed with glyoxylic acid (XXXIV) in the presence of Et3N to yield the nitro hydroxy acid (XXXV). Then, compound (XXXV) is reduced with H2 over Pd/C in MeOH and esterified with MeOH and p-TsOH·H2O to give amino ester (XXXVI). Finally, aminolysis of methyl ester (XXXVI) with NH3 and NH4OH in MeOH followed by N-protection by means of Boc2O and K2CO3 in MeOH/H2O yields intermediate (XXVII) .