Related Products of 6358-77-6, These common heterocyclic compound, 6358-77-6, name is 5-Bromo-2-methoxyaniline, 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.
Step 1. Synthesis of 1 -(5-bromo-2-methoxyphenyl)-5-methyl-1 H-pyrazole (C14). Boron trifluoride-tetrahydrofuran complex (777 g, 5.55 mol) was slowly added to a solution of 5-bromo-2-methoxyaniline (799.8 g, 3.96 mol) in 2-methyltetrahydrofuran (5.3 L), and the mixture was filtered through Celite. The filtrate was brought to a volume of 9 L with additional 2-methyltetrahydrofuran. In a separate container, tert-butyl nitrite (433 g, 4.20 mol) was dissolved in 2-methyltetrahydrofuran (8.0 L); the volume was then adjusted to 9 L by addition of 2-methyltetrahydrofuran. The two solutions were pumped by two Ismatec syringe pumps, both of which had been calibrated to deliver 15 mL/minute of 2-methyltetrahydrofuran, into a T-mixer connected to a 240 ml_ polytetrafluoroethylene (PTFE) coil for diazonium salt formation. At a combined flow rate of 30 mL/minute, the reaction mixture had a total residence time of 8 minutes in the coil to facilitate complete diazonium salt formation. The syringe pumps were started simultaneously, and the material was passed through the coil into a two-stage continuous flow stirred-tank reactor, where the 5-bromo-2-methoxybenzenediazonium tetrafluoroborate product (C12) was continuously extracted into water, using a water pump with a flow rate of 20 to 22.5 mL/minute. The aqueous layer was continuously separated in a stand pipe decanter, and then quenched into a jacketed 20 L reactor containing a mixture of tin(ll) chloride dihydrate (2.28 kg, 12.0 mol), 2- methyltetrahydrofuran (4 L) and water (4 L) at zero C. When the reduction had provided complete conversion to (5-bromo-2-methoxyphenyl)hydrazine (C13), as monitored by HPLC analysis, a solution of (3E)-4-(dimethylamino)but-3-en-2-one (454 g, 4.01 mol) in 2-methyltetrahydrofuran (3.0 L) was charged, and the jacket temperature was adjusted to 20 C. After 14 hours, analysis of the organic layer indicated that hydrazine C13 had been consumed. The layers were separated, and the organic layer was washed with aqueous sodium hydroxide solution (6 N, 2 x 5 L). Silica gel (1 .0 kg) was added to the organic phase, and the mixture was concentrated to dryness and dried at 35 C and 100 mbar vacuum on a rotary evaporator until a free-flowing powder was obtained. This powder was loaded onto a pad of silica gel (100 g), and elution was carried out with 2- methyltetrahydrofuran (6 L); the eluant was concentrated in vacuo to provide the product as a thick dark red oil. 1H NMR data indicated that this material was comprised of a roughly 9:1 ratio of the title product and the regioisomeric pyrazole. Yield: 573 g, 2.15 mol, 67% (corrected for 80% purity of starting 5-bromo-2-methoxyaniline). GCMS m/z 266, 268 (M+). 1H NMR (400 MHz, CDCI3) title product peaks only: delta 7.60 (d, J=1 .8 Hz, 1 H), 7.52 (dd, half of ABX pattern, J=8.7, 2.4 Hz, 1 H), 7.49 (d, half of AB pattern, J=2.4 Hz, 1 H), 6.92 (d, J=8.7 Hz, 1 H), 6.16-6.18 (m, 1 H), 3.79 (s, 3H), 2.16 (br s, 3H).
Statistics shows that 5-Bromo-2-methoxyaniline is playing an increasingly important role. we look forward to future research findings about 6358-77-6.
Reference:
Patent; PFIZER INC.; BRODNEY, Michael Aaron; WO2012/172449; (2012); A1;,
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