Dimethylformamide → Lithium diisopropylamide mono(tetrahydrofuran)

Participants

Reaction Conditions

Reaction Steps

An LDA/THF solution was prepared by adding n-BuLi (1.6 M/hexanes, 5.10 mL, 8.16 mmol, 1.5 equiv) to diisopropylamine (1.15 mL, 8.16 mmol, 1.5 equiv) in THF (15 mL) at −78° C. The reaction mixture was warmed to −20° C. and stirred for 15 min. After the LDA solution was cooled to −78° C., compound S1-6 (2.26 g, 5.44 mmol, 1.0 equiv) in THF (5 mL) was added dropwise. An orange-red solution was formed. After 10 min, DMF (1.26 mL, 16.30 mmol, 3.0 equiv) was added dropwise. The reaction solution was allowed to warm to −20° C. in 1 h and quenched by saturated aqueous NH4Cl. LC/MS indicated that the starting material was consumed. The reaction mixture was diluted with EtOAc (100 mL), washed with water and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. This gave 2.42 g of crude S1-7, which was purified by column chromatography (Biotage 24 g column, 5 to 10% EtOAc in hexanes gradient), yielding 2.23 g (92%) of the pure compound S1-7 as a light yellow solid: 1H NMR (400 MHz, CDCl3) δ 10.37 (s, 1 H), 7.51-7.47 (m, 2 H), 7.40-7.33 (m, 5 H), 7.27 (t, J=7.3 Hz, 1 H), 7.06-7.02 (m, 2 H), 5.12 (s, 2 H), 2.37 (d, J=2.3 Hz, 3 H).

Provenance & Evidence