Hydrazine hydrate (1:1) → HCID 61734338, compound

Participants

Reaction Conditions

Reaction Steps

(see, e.g., WO2009150614A1). To a solution of hydrazine monohydrate (hydrazine 78-82%) (0.51 ml, 10.5 mmol) in THF (2 mL), crotononitrile (mixture of cis and trans) (0.82 ml, 10.1 mmol) was added dropwise. The mixture was stirred at 40° C. for 2 h. The mixture was allowed to cool to room temperature and biphenyl-4-carboxaldehyde (1.82 g, 10.0 mmol) was added. The mixture was stirred at 40° C. for 2 h. The mixture was concentrated under reduced pressure. To the resulting yellow solid was added iPrOH (15 mL) and the suspension was transferred to a pressure vessel. t-BuONa (993 mg, 10.3 mmol) was added and the mixture was stirred at 100° 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 IN 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 (885 mg, 34% over three steps) as a yellow solid. Crude was used in the next reaction without further purification. 1H NMR (500 MHz, DMSO-d6) δ 7.68-7.61 (m, 4H), 7.45 (t, J=7.5 Hz, 2H), 7.39 (d, J=7.9 Hz, 2H), 7.37-7.33 (m, 1H), 5.59 (s, 1H), 5.38 (s, 2H), 2.20 (s, 3H). 13C NMR (125 MHz, DMSO-d6) δ 151.46, 146.77, 140.52, 139.98, 134.32, 129.40, 128.62, 128.09, 127.51, 127.14, 91.23, 48.92, 11.54.

Provenance & Evidence