The 3,3'-dihydoxycarbonyl-2,2'-bipyridine acid
1 used for the preparation of diastereoisomeric compounds
2a-b has been obtained by described method of Blau [
1].
Procedure A: To 10 mL of clean thionyl chloride (new bottle without further distillation), were added 600 mg (2.5 mmol) of 3,3'-dihydroxycarbonyl-2,2'-bipyridine
1 and the mixture was refluxed for 5 h. Then the excess of SOCl
2 was removed under vacuum to leave an unstable yellow residue [
1]. 20 mL of toluene and then 1 mL of MeOH were added and the solution was heated at reflux for 3 h. 40 mL of chloroform were added and the organic phase was washed with a cooled solution of sodium hydrogen carbonate (2.5%), and then dried on sodium sulfate. The crude product was chromatographed on silica column. Only compound
3 was obtained as product of reaction (55-60%); the rest is the unreacted stating material
1.
Procedure B: When we used an old bottle of SOCl
2, in the same conditions (procedure A), three white solids were successively obtained: a mixture of petroleum ether/dichloromethane 10/90 eluted first compound
2a (310 mg, 31 %), and then in the ratio 5/95 derivative
2b (70 mg, 7%) was recovered; and finally with ether/acetone 40/60, the diester
3 (450 mg, 52%) was eluted, which has been described elsewhere [
2].
Compound 2a: methyl (7S,8R,9S)-7,8,9-trichloro-5-oxo-5,7,8,9-tetrahydropyrido-[2,3-a] indolizine-10-carboxylate (Labelling used for NMR assignments)
m.p. = 121-122 °C; Analysis Calc. (Found) for C13H9N2O3Cl3: C 44.94 (44.98), H 2.59 (2.63), N 8.06 (7.99); Mass spectrum : m/z = 347.0 (Calc. for C13H9N2O3Cl3: 346.60); IR (KBr) n cm-1: 1744 (C=O, s), 1717 (C=O, s), 1601,1581 (C=C, w), 1434 (C=N, m), 1297 (C-O, w); 1H NMR (250.14 MHz; CDCl3) d ppm: 8.9 (dd, H2, 3JH2-H3 = 4.9 Hz, 4JH2-H4 = 1.6 Hz), 8.2 (dd, 1 H, H4,3JH4-H3 = 7.8 Hz,4JH4-H2 = 1.6 Hz), 7.53 (dd, 1 H, H3, 3JH3-H4 = 7.8 Hz, 3JH3-H2 = 4.9 Hz), 6.49 (dd, 1 H, H7, 3JH7-H8 = 1.33 Hz, 4JH7-H9 = 2.1 Hz), 5.35 (t, 1 H, H8, 3JH8-H7 = 1.33 Hz, 3JH8-H9 = 1.33 Hz), 5.03 (dd, 1 H, H9, 3JH9-H8 = 1.33 Hz,4JH7-H9 = 2.1 Hz), 4.0 (s, 3 H, CH3).
Compound 2b: methyl (7R,8R,9S)-7,8,9-trichloro-5-oxo-5,7,8,9-tetrahydropyrido-[2,3-a]-indolizine-10-carboxylate
Mass spectrum : m/z = 347.0 (Calc. for C13H9N2O3Cl3: 346.60); 1H NMR (200.131 MHz; CDCl3) d ppm: 8.86 (dd, 1 H, H2, 3JH2-H3 = 4.9 Hz, 4JH2-H4 = 1.6 Hz), 8.14 (dd, 1 H, H4, 3JH4-H3 = 7.8 Hz, 4JH4-H2 = 1.6 Hz), 7.48 (dd, 1 H, H3, 3JH3-H4 = 7.8 Hz, 3JH3-H2 = 4.9 Hz), 6.47 (d,1 H, H8, 3JH8-H9 = 3 Hz), 5.26 (d, 1 H, H10, 3JH10-H9 = 9.8 Hz), 4.52 (dd, 1 H, H9, 3JH9-H8 = 3.05 Hz, 3JH9-H10 = 9.75 Hz), 3.96 (s, 3H, CH3).