Generation and Reactions of Heteroaromatic Lithium Compounds by Using In-Line Mixer in a Continuous Flow Microreactor System at Mild Conditions

Abstract

HNMR spectra 13 C-NMR spectra were recorded on JEOL ECA NMR spectrometer (1 H 400 MHz, 13 C 100 MHz). HPLC analysis was performed on Agilent 1200 (DAD: 254 nm, column: agilent zorbax eclipse XDB-C18 (4.6×150 mm, I.D. 5 µm)). ESI mass spectra were recorded on Bruker micrOTOF II. All reagents were obtained from

Development and Scale-up of a Flow Chemistry Lithiation–Borylation Route to a Key Boronic Acid Starting Material

“…An alternative route for a key boronic acid starting material was investigated utilizing flow flash chemistry , techniques, and a lithiation–borylation process that was difficult if not impossible to control in batch was successfully developed into a kilo-scale process. Although the cost of raw materials for the route was found to be greater than for the Miyaura borylation batch process using BBA, the flow process had potential benefits arising from avoiding the use of Pd and potentially mutagenic boron reagents, such as BBA or B 2 Pin 2 .…”

The Hitchhiker’s Guide to Flow Chemistry

“…Liu et al found similar enhancements for the functionalization of other heteroaromatic compounds using a split and recombine mixer in flow. 503 Lithiation of 2-bromopyridine 206 and quenching with methanol was used as a model reaction for the optimization of the flow setup. In batch, the yield of pyridine was below 50% at −40 °C and dropped by nearly half after warming to 20 °C.…”

Synthesis of Organometallic Compounds in Flow

“…Jia and coworkers reported the functionalization of bromo‐heterocycles through Br−Li exchange conducted at 10 °C using a similar approach . In this case, the mixing efficiency was increased by a stainless steel in‐line mixer ( IM1 ) which is a splitting‐and‐recombining type micromixer, introduced after the first micromixer ( M1 ; Figure ).…”