2-Bromo-2-methylpropanoic acid → Pyrazole

Participants

Reaction Steps

Scheme 7 shows the synthesis of ethyl 2-(4-bromo-1H-pyrazol-1-yl)-2-methylpropanoate IV starting from 2-bromo-2-methylpropanoic acid 15. Alkylation of pyrazole with 15 gave 2-methyl-2-(1H-pyrazol-1-yl)propanoic acid 16 (Example 12). Esterification of 16 with sulfuric acid in ethanol gave ethyl 2-methyl-2-(1H-pyrazol-1-yl)propanoate 17 (Example 13). Regiospecific bromination of 17 with N-bromosuccinimide (NBS) gave IV (Example 14). Alternatively, 16 was treated in situ with a brominating reagent such as 1,3-dibromo-5,5-dimethylhydantoin (DBDMH) to give 2-(4-bromo-1H-pyrazol-1-yl)-2-methylpropanoic acid which was esterified to give IV, where R is ethyl. Other esters can also be prepared, such as methyl, iso-propyl, or any alkyl, benzyl or aryl ester.

Provenance & Evidence