methyl 5-chloro-2,3-dihydro-1H-indole-2-carboxylate

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

Procedure: Methyl 5-chloroindoline-2(R/S)-carboxylate (0.63 g, 3 mmol) was dissolved in butylamine (25 ml) and refluxed for 4 h. The excess amine was removed and the residue was crystallized from ether to give a yellow solid. refluxed for 4 h The excess amine was removed the residue was crystallized from ether to give a yellow solid

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

Procedure: Methyl 5-chloroindole-2-carboxylate (0.6 g, 2.87 mmol) and magnesium shavings (0.34 g, 14.3 mmol) were suspended in methanol (40 ml) and the mixture was stirred for 8 h. The mixture was filtered, treated with methylene chloride (100 ml) and washed with NH4Cl solution. The organic fraction was dried (Na2SO4) and the solvent removed in order to give a solid which was purified by chromatography on a column of silica gel, using a 7/3 petroleum/ethyl acetate mixture as eluent. The product was isolated in the form of a yellow solid. The mixture was filtered treated with methylene chloride (100 ml) washed with NH4Cl solution The organic fraction was dried (Na2SO4) the solvent removed in order to give a solid which was purified by chromatography on a column of silica gel The product was isolated in the form of a yellow solid

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

Procedure: This compound was prepared from ethyl 5-chloroindole-2-carboxylate as described in example 1. However this time 5-6 equivalence of magnesium turnings were used instead of 2-3 eq. of magnesium turnings.

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

Procedure: To a solution of 5-chloroindoline-2(R/S)-carboxylic acid methyl ester (1.2 g, 5.69 mmol) and N-t-butoxycarbonyl-2(S)-aminobutyric acid (1.27 g, 6.25 mmol) dissolved in dried dichloromethane (10 ml) under nitrogen at 10° C., was added diisopropylcarbodiimide (0.98 ml, 6.30 mmol). The mixture was stirred at room temperature for 24 hours, then filtered. The filtrate was evaporated under vacuum to afford a brown solid which was purified by column chromatography on silica gel using 20:1 dichloromethane: diethyl ether as eluent. A white foam was obtained which was the mixture of two diastereomers. The two diastereomers were separated by column chromatography on silica gel using 7:3 petroleum spirit:diethyl ether as eluent, and the pure (S,S) form was obtained as a white foam. filtered The filtrate was evaporated under vacuum to afford a brown solid which was purified by column chromatography on silica gel using 20:1 dichloromethane A white foam was obtained which the mixture of two diastereomers The two diastereomers were separated by column chromatography on silica gel using 7:3 petroleum spirit diethyl ether as eluent, and the pure (S,S) form was obtained as a white foam