methyl 4-(3-methylbutanoyl)-1H-pyrrole-3-carboxylate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methyl 4-(3-methyl-1-oxobutyl)-1H-pyrrole-3-carboxylate (Example 1, step b, 7.8 g) and methylhydrazine (6 ml) were heated at reflux for 18 hours. The solvent was evaporated and the residue was chromatographed, eluting with dichloromethane-ethanol (19:1), to give the sub-title compound as a sand coloured solid (5.2 g). at reflux for 18 hours The solvent was evaporated the residue was chromatographed eluting with dichloromethane-ethanol (19:1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To sodium hydride (0.42 g of a 60% oil dispersion, 0.0105 mol), freed from oil, stirred in dry dimethyl formamide (15 ml) under nitrogen was added methyl 4-(3-methyl-1-oxobutyl)-1H-pyrrole-3-carboxylate (2.2 g) prepared as described in b) above in portions over 20 minutes. After 10 minutes, potassium iodide (0.01 g) and (1-naphthalenyl)methyl chloride (1.85 g) in dimethyl formamide (20 ml) were added. The mixture was stirred for 4 hours and then poured into 0.5M hydrochloric acid and extracted with ethyl acetate. The organic layer was washed well with water and then brine, dried and evaporated to a gum, which was chromatographed with ethyl acetate-isohexane (1:3) to give an oil. The oil was crystallised from cyclohexane to yield the subtitle pyrrole (2.6 g). prepared over 20 minutes extracted with ethyl acetate The organic layer was washed well with water brine, dried evaporated to a gum, which was chromatographed with ethyl acetate-isohexane (1:3) to give an oil The oil was crystallised from cyclohexane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of (E)-methyl 6-methyl-4-oxo-2-heptenoate (10 g) prepared as described in a) above and (para-toluenesulfonyl)methyl isocyanide (11.5 g) in a mixture of dry dimethyl sulfoxide (30 ml) and diethyl ether (30 ml) was added over one hour to sodium hydride (2.75 g of a 60% oil dispersion, 0.068 mol) stirred in dry diethyl ether (90 ml) under nitrogen. After a further hour saturated ammonium chloride solution was added and the mixture was extracted with ethyl acetate, which was washed well with water, dried, and evaporated to a gum. The gum was chromatographed with ethyl acetate-isohexane (2:3) to afford a solid (3.3 g) which was crystallised from ethyl acetate-cyclohexane to give the sub-title ester. the mixture was extracted with ethyl acetate, which was washed well with water dried evaporated to a gum The gum was chromatographed with ethyl acetate-isohexane (2:3)