Synthesis of 4-Ethoxy-2,3-dihydropyridinium Tetrafluoroborate Salts and 4-Ethoxy-2,3-dihydropyridines

Abstract

Transformation of 2,3-dihydropyridones to 2,3-dihydropyridinium tetrafluoroborate salts and 2,3-dihydropyridines was accomplished using ethyl Meerwein’s reagent.

Key words

dihydropyridine - pyridine - Meerwein’s Reagent - hydrogenations - reductions

References and Notes

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6

N -Carbobenzyloxy-4-ethoxy-2,3-dihydropyridinium Tetrafluoroborate (3a): An oven-dried, argon-purged 5-mL conical vial was charged with N-carbobenzyloxy-2,3-dihydropyrid-4-one (462.9 mg, 2 mmol). To this was added freshly prepared solution of ethyl Meerwein’s reagent in CH₂Cl₂ (2 mL, 2 mmol, 1 M) at r.t. The reaction mixture was stirred at r.t. and followed by NMR until the reaction was complete (2 d). Attempts to purify the material led to decomposition. ^¹H NMR (300 MHz, CDCl₃): δ = 8.86 (d, J = 6.9 Hz, 1 H), 7.23-7.36 (m, 5 H), 6.10 (d, J = 6.9 Hz, 1 H), 5.52 (s, 2 H), 4.49 (q, J = 7.0 Hz, 2 H), 4.21 (t, J = 8.7 Hz, 2 H), 3.00 (t, J = 8.7 Hz, 2 H), 1.42 (t, J = 7.0 Hz, 3 H).

8

4-Ethoxy-2,3-dihydropyridine (4a): An oven-dried, argon-purged 50-mL round-bottom flask was charged with 2,3-dihydropyrid-4-one (884.6 mg, 9.1 mmol), and Na₂HPO₄ (1.55 g, 10.9 mmol). To this was added freshly distilled CDCl₃ (10 mL). A solution of ethyl Meerwein’s reagent in CDCl₃ (9.1 mL, 9.1 mmol, 1 M) was then added at r.t. The reaction mixture was stirred at r.t. and followed by NMR until the reaction was complete (2 d). The reaction mixture was then filtered to remove the phosphates and concentrated in vacuo. Further purification attempts led to decomposition. ^¹H NMR (300 MHz, CDCl₃): δ = 8.29 (d, J = 5.7 Hz, 1 H), 5.68 (d, J = 5.7 Hz, 1 H), 4.20 (q, J = 7.0 Hz, 2 H), 3.89 (t,
J = 9.3 Hz, 2 H), 2.76 (t, J = 9.3 Hz, 2 H), 1.20 (t, J = 7.0 Hz, 3 H). ^¹³C NMR (300 MHz, CDCl₃): δ = 179.6, 166.2, 92.5, 66.2, 40.9, 27.3, 15.7. HRMS: m/z calcd for C₇H₁₁NO: 125.0841; found: 125.0842.