Tetrahydrofuran → HCID 61733729, compound

Participants

Reaction Conditions

Reaction Steps

(see, e.g., Misra, R. N., et al., Bioorg Med Chem Lett 2003, 13, 1133-6). To a solution of hydrazine monohydrate (hydrazine 78-82%) (0.80 ml, 16.5 mmol) in THF (3 mL), crotononitrile (mixture of cis and trans) (1.1 ml, 13.5 mmol) was added dropwise. The mixture was stirred at 40° C. for 2 h. The mixture was allowed to cool to room temperature and 3-phenoxybenzaldehyde (2.14 ml, 12 mmol) was added dropwise. The mixture was stirred at 40° C. for 2 h. The mixture was concentrated under reduced pressure. To the resulting intermediate was added nPrOH (10 mL) and the suspension was transferred to a pressure vessel. t-BuONa (1.41 g, 14.7 mmol) was added and the mixture was stirred at 110° C. for 2 h 30 min. The mixture was allowed to cool to room temperature and diluted with water (50 mL). The mixture was extracted with Et2O (50 mL×2). The combined organic layers were extracted with 1N aq. HCl (2×30 mL). The combined aqueous phases were basified to pH 14 with 50% aq. NaOH and extracted with Et2O (50 mL×2). The combined organic layers were washed with brine, dried (Na2SO4), filtered, and concentrated under reduced pressure to provide the title compound (670 mg, 20% over three steps) as an orange oil. Crude was used in the next reaction without further purification. 1H NMR (500 MHz, CDCl3) δ 7.32 (t, J=7.0 Hz, 2H), 7.25 (t, J=7.8 Hz, 1H), 7.10 (t, J=6.9 Hz, 1H), 6.98 (d, J=7.8 Hz, 2H), 6.85 (t, J=7.6 Hz, 2H), 6.80 (s, 1H), 5.37 (d, J=2.6 Hz, 1H), 5.10 (s, 2H), 2.17 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 157.81, 156.75, 147.74, 145.05, 139.08, 130.19, 129.75, 123.46, 121.22, 119.04, 117.63, 116.99, 91.65, 50.86, 13.92.

Provenance & Evidence