Ethyl 2-methylacetoacetate → ethyl 5-methyl-1H-indole-2-carboxylate

Participants

Reaction Conditions

Reaction Steps

15.4 g of NaNO2 in 4 ml of water are added, at 0° C., to 23.57 g of p-toluidine in 50 ml of HCl and 100 ml of water; after stiring for 20 minutes, 18.2 g of sodium acetate ate added. Separately, a mixture of 28.8 g of ethyl 2-methyl-3-oxobutyrate in 100 ml of ethanol is prepared, at 0° C, and is treated with 11.22 g of potassium hydroxide in20 ml of water and 200 g of crushed ice. The diazonium salt solution prepared above is added and the mixture is left stirring for 3 hours at 0° C. After leaving overnight in a refrigerator, it is poured onto saturated NaCl solution and is then extracted with EtOAc, dried over MgSO4 and concentrated. The residue is taken up in toluene, 16 g of para-toluenesulphonic acid are added and the mixture is refluxed overnight, eliminating the water using Dean-Stark apparatus. The reaction medium is chromatographed on silica, eluting with toluene, to give 12 g of the expected product: m.p.=133° C.

Provenance & Evidence