Application of 40872-87-5, In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 40872-87-5, name is Methyl 3-amino-4-chlorobenzoate belongs to esters-buliding-blocks compound, it is a common compound, a new synthetic route is introduced below.
EXAMPLE 3 Synthesis of 3-cyclopentyl-1-methyl-2-pyridin-2-yl-1H-indole-6-carboxylic acid methyl ester (13) A 100 mL three neck flask equipped with a thermocouple, condenser and stir bar was purged with argon. 3-Amino-4-chlorobenzoic acid methyl ester (5.0 g, 26.94 mmol), 2-cyclopentylethynyl-pyridine (5.528 g, 32.33 mmol), Pd(OAc)2 (181 mg, 0.81 mmol), DtBPF (767 mg, 1.62 mmol), K2CO3 (9.29 g, 67.35 mmol) and NMP (25 mL) were then charged. The reaction was heated to 130 C. and monitored by HPLC. The reaction was complete after 6 hours. The reaction was cooled to room temperature. DMC (11.4 mL, 134.69 mmol) and tetrabutylammonium bromide (TBAB) (0.868 g, 2.69 mmol) were added. The mixture heated to 130 C. HPLC showed less than 3% starting material remaining after 4.5 h. The mixture was filtered through a pad of diatomaceous earth. The black cake was washed with i-PrOAc (50 mL). Solution yield of this mixture was 78%. The crude product residue was dissolved in i-PrOAc (50 mL). The solution was washed with 0.3 N aqueous HCl three times (20 mL, then 2*15 mL). The organic phase was concentrated under vacuum. Propanol, water and 50% NaOH were added to the above residue. The reaction was heated to 90 C. for 1 h. HPLC showed that the reaction was complete. After the mixture was cooled to 50-60 C., diatomaceous earth and activated carbon were added. The mixture was stirred at 50 C. for 30 min and filtered to a 100 mL three neck flask through a pad of diatomaceous earth. The wet cake was washed with 18 mL of water/1-propanol 9/1. The mixture was then heated to 50 C. Acetic acid was added dropwise at this temperature. Precipitation was observed upon the addition. The suspension was then heated to reflux and held for 30 min. The mixture was slowly cooled to room temperature for 2 hours. The precipitate that formed was filtered. The wet cake was washed with 10 mL 1-propanol/water (2:1). The yellow solid was dried under vacuum for 2 days. 5.6 g product was obtained. The yield was 62% for three steps with 99.32 A % purity. 1H NMR (300 MHz, DMSO-d6) delta 8.80 (d, J=3.0 Hz, 1H), 8.14 (s, 1H), 8.00 (m, 1H), 7.77 (d, J=6.0 Hz, 1H), 7.69 (d, J=9.0 Hz, 1H), 7.59 (d, J=6.0 Hz, 1H), 7.50 (m, 1H), 3.89 (s, 3H), 3.70 (s, 3H), 3.17-3.11 (m, 1H), 1.90-1.60 (m, 8H).
The synthetic route of Methyl 3-amino-4-chlorobenzoate has been constantly updated, and we look forward to future research findings.
Reference:
Patent; Boehringer Ingelheim International GmbH; US2005/209465; (2005); A1;,
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