Dimethylformamide → Lithium diisopropylamide mono(tetrahydrofuran)

Temperature

-20 °C

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).

1. customAn orange-red solution was formed
2. waitAfter 10 min
3. temperatureto warm to −20° C. in 1 h
4. customquenched by saturated aqueous NH4Cl
5. customwas consumed
6. additionThe reaction mixture was diluted with EtOAc (100 mL)
7. washwashed with water and brine
8. dry with materialdried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customThis 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)

ORD record

ord-96dfaee26a4040cb94bc14b9d3889cd1

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09315451B2