Aluminium lithium hydride → HCID 44546894, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of Compound 25 (51 mg, 0.15 mmol) in THF (8 mL) at 0° C. was added lithium aluminum hydride (0.6 mL, 1 M in THF) dropwise. After the addition, the reaction solution was heated under reflux for 1 h, cooled to 0° C. and quenched by sequential addition of water (1.8 mL), aqueous sodium hydroxide (0.6 mL) and water (0.6 mL). The resultant mixture was stirred at 0° C. for 10 min before it was filtered. The filtrate was extracted with dichloromethane (2×). The combined organic extract was dried over sodium sulfate and concentrated in vacuo. Purification by preparative thin layer chromatography (dichloromethane/methanol/concentrated ammonia 95:4.5:0.5) provided Compound 7 (32.0 mg, 70%, AUC HPLC 96.8%, Chiralpak AD 100%) as a light yellow oil: [α]23D +50.7° (c 0.18, methanol); 1H NMR (500 MHz, CDCl3) δ 7.79-7.68 (m, 3H), 7.68 (s, 1H), 7.47-7.43 (m, 2H), 7.28-7.26 (m, 1H), 6.80 (d, J=8.0 Hz, 1H), 6.65-6.62 (m, 2H), 4.39 (dd, J=8.5, 6.0 Hz, 1H), 3.78 (s, 3H), 3.77 (d, J=15.0 Hz, 1H), 3.65 (d, J=14.5 Hz, 1H), 3.09 (dd, J=11.5, 5.5 Hz, 1H), 2.64 (dd, J=11.5, 9.0 Hz, 1H), 2.44 (s, 3H); ESI MS m/z 304 [M+H]+. This compound co-elutes with authentic Compound 7 on Chiralpak AD (90:10:0.1 heptane: IPA: diethyl amine, 1 mL/min, RT=14.3 min. The RT of the (−)-enantiomer of Compound 7=6.2 min).

Provenance & Evidence