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Patent / 1989

Rhodium hydrogenation catalysts particularly for stereoselective hydrogenation of methacycline to doxycycline

Plurichemie Anstalt

Authors:
  • William Heggie
  • Ivan Villax
  • Indira Ghatak
  • Michael Hursthouse
Source:
EP 283616
Homogeneous catalyst systems including I and II are prepd. for use in stereoselective hydrogenation of methacycline to the bactericide doxycycline. Rh(NO3)3.2H2O 1.18, PPh3 4.27, and hydrazine 3.36 mmol in MeOH (10 mL of a 10.77 mg/mL soln) were refluxed overnight under N in MeOH and large orange crystals of II obtained, for which the crystal structure was detd. (parameters given). Methacycline 21.7 mmol was suspended in MeOH 84.5 mL in a stainless steel high-pressure reaction vessel to which II 0.017 mmol was added. The vessel was purged under N and pressurized to 8 kg/cm2 with H. The reaction was performed at 88.degree. for 6.5 h with stirring. The H was discharged and p-toluenesulfonic acid 24.2 mmol was added; after stirring for 2 h, the resulting doxycycline p-toluenesulfonate 12.0 g was obtained by filtering, washing with MeOH and drying at 35.degree.; the product yield was 89.8% and the product, as shown by HPLC, was 99.2% pure.