Indole → 1-Methylindole

The R group can be at any position of the indole system except position 1. The reaction between indole-3-carboxylic acids and dimethyl carbonate was also investigated. The selectivity between O-methylation and N-methylation was not as high as would be expected. However, as expected, under the reaction conditions, esterfication of a carboxyl group was somewhat faster than N-methylation. For example, the reaction of indole-3-propionic acid with dimethyl carbonate in the presence of potassium carbonate in OMF afforded both an O,N-dimethylated substance in 65% yield after 4 hours at refluxing temperature, together with 30% of the O-methylated product. After the reaction mixture was heated to reflux for another 4 hours, only O,N-dimethylated product was obtained in 93% isolated yield. As demonstrated in Table 2, similar results were observed with indole-3-acetic acid. But when indole-3-carboxylic acid was subjected to the typical reaction conditions, along with 50% of the dimethylated product obtained, 45% of N-methylindole was isolated, formed as a result of decarboxylation of indole-3-carboxylic acid at the reaction temperature (128° C.).

1. customHowever, as expected, under the reaction conditions, esterfication of a carboxyl group
2. customafforded both an O,N-dimethylated substance in 65% yield after 4 hours
3. temperatureat refluxing temperature
4. temperatureAfter the reaction mixture was heated
5. temperatureto reflux for another 4 hours
6. customonly O,N-dimethylated product was obtained in 93%
7. customisolated
8. customyield
9. customsimilar results
10. customobtained

ORD record

ord-f1b2ccfee012458ea97bc636e1de84c1

Source dataset

uspto-grants-2001_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06326501B1