抗生素中间体中合成过程检测方案(化学合成仪)

FlowSynTM Application Note 8：Scale-up Synthesis of a ZyvoxTM Intermediate Objective： ZyvoxTM (Upjohn) was the first example of a new class of oxazolidinone antibiotics that are activeagainst MRSA. In this example， the scale-up abilities of FlowSynTM are demonstrated byperforming the first step in a possible synthesis of this compound on a 100 g scale. Method： System solvent： Dimethylformamide.Stock solution A： 2.0 M 3，4-Difluoronitrobenzene 1 (55.0 mL， 0.50 mol) in DMF (195 mL). Stock solution B： 4.0 M Morpholine 2 (87.0g， 0.75 mol) in DMF (163 mL). A 45 psi fixed back-pressure regulator was fitted and used in all experiments. Flow Scale-up using Start Experiment'Interface FlowSynTM is equipped with a program that allows unattended operation and is able to run a flowexperiment automatically， stopping and cleaning the instrument when the reaction is complete. 1.FlowSynTM was fitted with a 20 mL SS tubing reactor cassette， and the heating unit wastensioned to ensure optimal thermal contact. 2.A 40 psi fixed BPR was connected in-line to the outflow from the tubing reactor before thecollection valve 3.The Collect'outflow from the collection valve was directed into a 5 L Duran collection bottlecontaining water (4 L) mounted on a stirrer. 4.The selection valves were set to 'Reagent' and the reagent lines were primed up to the valves. 5.The selection valves were set to `Solvent' and the solvent lines were primed. 6.The pumps were started at 4.0 mL/min to rapidly prime the system with solvent and remove allair bubbles (indicated by a stable pressure reading). The pumps were calibrated at 1.00 mL/minas previously [no further adjustments were necessary]. 7.The following flow parameters were entered into the 'Setup Experiment' screen. Reactors： Coil Reaction Time： 8.00 min (00：08：00) Coil Type： User Total Flow Rate： 2.50 mL/min Coil Volume： 20 mL Volume A： 225 mL (0.45 mol) Coil Temp：100°CVolume B：225 mLCol. Temp.0°CA：B Ratio：1.0：1.0 Pressure： Auto Post Collect： 25.0 mL Inlet A： RPost Wa sh： 20.0 mLR Inlet B： Reaction time = 3.00 h. 8.Upon pressing `Run Experiment'， FlowSynTM equilibrates to the set temperature and then runsthe flow experiment， before finally cleaning the system by flushing with system solvent (`PostWash'). 9.The precipitated reaction product was collected by filtration， washed with water (3 x 100 mL)，then air-dried before drying o/n @ 50°C in vacuo to afford the nitro-aniline 3 as a free-flowingyellow powder (101 g， 99%)： m.p.=113-115℃ Throughput = 0.15 mol/h (34 g/h). 'H NMR (CDCl3， 400 MHz)： 8-7.20-7.30 (m， 8H)， 7.10-7.15 (m， 2H)， 6.70 (s， 1H). Supplementary Information： Figure 2. Schematic FlowSynTM configuration used. -- --