20265-97-8, A common heterocyclic compound, 20265-97-8, name is 4-Methoxyaniline hydrochloride, molecular formula is C7H10ClNO, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
General procedure: Three stock solutions were prepared and connected to the flow reactor feed lines for Pumps A-C (see Figure 3 for a pictorial layout). Pump A delivered hydrochloric acid (0.84 M), Pump B a solution of aqueous sodium nitrite (0.98 M) and pump C delivered an aqueous solution of ascorbic acid (0.35 M). In addition a further pump was used to provide the solutions of aniline as their HCl salts dissolved in water (0.35 M). The entire reactor was maintained under positive internal pressure using a 75 psi back pressure regulator at the exit of the reactor. To initiate the reaction each flow channel was pumped at 0.5 mL/min. Progressing through the reactor; Channel A and B were mixed in a Uniqsis mixer chip of 0.27 mL internal volume (16 s residence time) before passing into a 2.75 mL PFA tubular residence coil (165 s residence time). The combined flow was then further united with the aniline solution mixing in a second Uniqsis mixer chip of 2 mL internal volume (80 s residence time). The reacting solution then passed into a 5 mL residence PFA foil coil (150 s residence time, the solution turns pale yellow to orange). The whole initial stage mixing unit was temperature regulated (10 C) using a Polar Bear Plus flow reactor unit. In the second stage reactor the freshly prepared diazonium mixture (combined flow rate 2 mL/min) was united at an Upchurch peek T-mixer with a solution of ascorbic acid delivered from Pump C set at 0.5 mL/min. The flow stream was then progressed into a 52 mL PFA flow coil (20.8 min residence time).The isolation of certain intermediate hydroxamic esters, namely 13-18, could be achieved by immediate extraction of the reactor output with ethyl acetate (5 volumes) and washing the organic phase with sodium hydrogen carbonate (2 M; 2). The organic solution was dried over MgSO4, filtered and concentrated in vacuo to provide a pale yellow solid which was triturated with a 1:1 mixture of hexane and acetone to furnishing the desired product. Alternatively, the output solution was collected and left to stir for 1 h to ensure complete hydrolysis to the corresponding oxamic acid, 1-12, had occurred. The products were isolated by basification of the reaction mixture pH ~9 followed by extraction with EtOAc (3 volumes). The aqueous solution was then acidified to pH ~4 and extracted with EtOAc (3 volumes), the organic phase was dried over MgSO4, the solvent evaporated to yield compounds 1-12. Note: for compounds 1-12 a proton signal sites under the residual DMSO signal.
The synthetic route of 4-Methoxyaniline hydrochloride has been constantly updated, and we look forward to future research findings.
Reference:
Article; Hu, Te; Baxendale, Ian R.; Baumann, Marcus; Molecules; vol. 21; 7; (2016);,
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