filtrate was neutralized with saturated NaHCO3 aqueous solution and then acetone was evaporated in
vacuo. The aqueous solution was extracted with EtOAc (5 mL x 3) and the combined extracts were
washed with saturated NaHCO3 aqueous solution (5 mL x 3) and brine (5 mL x 3) and then dried over
anhydrous Na2SO4. Concentration in vacuo gave crude crystals, which were recrystallized from
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25
hexane-EtOAc to give 11 as colorless needles. Yield 90% (62 mg). mp 158-160 C. [α]D –9.3o (c
0.67, MeOH). IR (KBr) 3448, 2980, 1785, 1728, 1707, 1656, 1521 cm-l. 1H NMR: δ 1.53 (s, 9H,
Boc’s t-Bu), 2.32-2.44 (m, 1H, H-4a), 2.96-3.08 (m, 1H, H-4b), 3.81 (s, 3H, COOCH3), 4.23-4.33 (m, 1H,
H-5), 5.10 (s, 2H, Cbz’s CH2), 5.83 (br d, 1H, NH, J=4.5 Hz), 6.51 (dd, 1H, H-3, J=2.6, 7.6 Hz), 7.37 (s,
5H, Ph). Anal. Calcd for C20H24N2O7: C, 59.40; H, 5.98; N, 6.93. Found: C, 59.34; H, 5.99; N, 7.32.
Methyl (5S)-Benzyloxycarbonylamino-6-oxo-1,4,5-trihydropyridine-2-carboxylate (12). A solution
of 11 (2.255 g, 5.58 mmol) in a mixture of CHCl3 and TFA (1 : 1 v/v, 30 mL) was stirred for 1 h at rt.
The reaction mixture was made to weak alkali with Et3N and then the solvent was evaporated in vacuo.
The residual substance was dissolved in EtOAc (50 mL) and the resulting solution was washed
successively with 10% citric acid (25 mL x 2), brine (25 mL x 3), and saturated NaHCO3 aqueous
solution (25 mL x 3) and then dried over anhydrous Na2SO4. Concentration in vacuo gave crude crystals,
which were recrystallized from a EtOAc-hexane to give 12 as colorless needles. Yield 99 % (1.697 g).
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mp 111-112 C. [α]D –40.2o (c 0.86, MeOH). IR (KBr) 3448, 3334, 1716, 1683, 1536 cm-l. 1H
NMR: δ 2.33 (ddd, 1H, H-4a, J=2.9, J=14.7, 17.6 Hz), 3.05 (ddd, 1H, H-4b, J=7.2, 7.3 Hz, 17.6 Hz), 3.81
(s, 3H, COOCH3), 4.28 (ddd, 1H, H-5, J=5.5, 7.3, 14.7 Hz), 5.11 (s, 2H, Cbz’s CH2), 5.96 (br d, 1H,
CbzNH, J=5.5 Hz), 6.27 (dd, 1H, H-3, J=2.9, 7.2 Hz), 7.33 (s, 5H, Ph), 7.92 (br s, 1H, H-1). Anal.
Calcd for C15H16N2O5: C, 59.21; H, 5.30; N, 9.21. Found: C, 58.94; H, 5.13; N, 8.97.
Methyl 5-Benzyloxycarbonylamino-6-oxo-1-hydropyridine-2-carboxylate (13). A suspension of 12
(0.50 g, 1.64 mmol) and MnO2 (4.28 g, 49.29 mmol) in CHCl3 (20 mL) was stirred under sonication for 6
h at rt. The MnO2 was filtered off and the residue was concentrated in vacuo to give crude crystals.
Recrystallization from a EtOAc-hexane gave 13 as colorless needles. Yield 80% (397 mg). mp
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185-186 C. IR 3430, 3404, 1737, 1716, 1650, 1632, 1569, 1524 cm-l. 1H NMR: δ 3.39 (s, 3H,
COOCH3), 5.22 (s, 2H, Cbz’s CH2), 7.10 (d, 1H, H-3, J=7.6 Hz), 7.37 (s, 5H, Ph), 8.10 (d, 1H, H-4, J=7.6
Hz), 8.13 (br s, 1H, CbzNH), 10.18 (br s, 1H, H-1). Anal. Calcd for C15H14N2O5: C, 59.60; H, 4.67; N,
9.27. Found: C, 59.55; H, 4.29; N, 9.15.
Methyl 5-Benzyloxycarbonylamino-6-methoxypyridine-2-carboxylate (14). A suspension of 13 (320
mg, 0.84 mmol), Ag2CO3 (116 mg, 0.42 mmol), and MeI (0.1 mL, 1.68 mmol) in CHCl3 (15 mL) was