ethyl (E)-5-methylhex-2-enoate

Conditions: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-Benzyl-N-(methoxymethyl)trimethylsilylmethylamine (2.84 g, 12 mmol), followed by TFA (1.0 M solution in CH2Cl2, 1.0 mL, 1 mmol) were added to a solution of (E)-5-methyl-hex-2-enoic acid ethyl ester (1.56 g, 10.0 mmol) in methylene chloride (30 mL) maintained at −5° C. under nitrogen atmosphere. After 15 minutes, the bath was removed and stirring was continued overnight. Saturated sodium bicarbonate was added, and the organic portion was separated, washed with brine, and dried. The product was purified by chromatography on silica gel, and compound was eluted with 20% ethyl acetate in hexane to give (trans)-1-Benzyl-4-isobutyl-pyrrolidine-3-carboxylic acid ethyl ester 3 as an oil (1.28 g, 44%). the bath was removed was continued overnight Saturated sodium bicarbonate was added the organic portion was separated washed with brine dried The product was purified by chromatography on silica gel, and compound was eluted with 20% ethyl acetate in hexane

Conditions: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-Benzyl-N-(methoxymethyl)trimethylsilylmethylamine (2.84 g, 12 mmol), followed by TFA (1.0 M solution in CH2Cl2, 1.0 mL, 1 mmol) were added to a solution of (E)-5-methyl-hex-2-enoic acid ethyl ester (1.56 g, 10.0 mmol) in methylene chloride (30 mL) maintained at −5° C. under nitrogen atmosphere. After 15 minutes, the bath was removed and stirring was continued overnight. Saturated sodium bicarbonate was added, and the organic portion was separated, washed with brine, and dried. The product was purified by chromatography on silica gel, and compound was eluted with 20% ethyl acetate in hexane to give (trans)-1-Benzyl-4-isobutyl-pyrrolidine-3-carboxylic acid ethyl ester 3 as an oil (1.28 g, 44%). the bath was removed was continued overnight Saturated sodium bicarbonate was added the organic portion was separated washed with brine dried The product was purified by chromatography on silica gel, and compound was eluted with 20% ethyl acetate in hexane

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

Procedure: In 15 ml of ethanol was dissolved ethyl (E)-5-methyl-2-hexenoate, to which was added 0.50 g of 5% palladium-carbon. Under a stream of hydrogen, the mixture was stirred at ambient temperature for 2 hours. The reaction mixture was filtered with Celite, and the solvent was distilled off under reduced pressure. Thus, 2.2 g of ethyl 5-methylhexanoate was obtained as a colorless oily product. The reaction mixture was filtered with Celite the solvent was distilled off under reduced pressure

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

Procedure: In Synthesis 1989, 953 a synthesis of rac.-Pregabalin, starting from (E)-5-methyl-hex-2-enoic acid ethyl ester, which was converted with nitromethane into 5-methyl-3-nitromethyl-hexanoic acid ethyl ester, has been reported. Subsequent catalytic hydrogenation followed by saponification leads to rac.-Pregabalin. Recently an enzymatic hydrolysis of this racemic nitro ester was carried out (Tetrahedron Asymmetry 2008, 19, 945). With enzyme Novozyme 435 enantiomerically enriched (S)-5-methyl-3-nitromethyl-hexanoic acid could be obtained in a good selectivity if the conversion was stopped at 30%. In Synthesis 1989, 953 a synthesis of rac

Conditions: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-Benzyl-N-(methoxymethyl)trimethylsilylmethylamine (2.84 g, 12 mmol), followed by TFA (1.0 M solution in CH2Cl2, 1.0 mL, 1 mmol) were added to a solution of (E)-5-methyl-hex-2-enoic acid ethyl ester (1.56 g, 10.0 mmol) in methylene chloride (30 mL) maintained at −5° C. under nitrogen atmosphere. After 15 minutes, the bath was removed and stirring was continued overnight. Saturated sodium bicarbonate was added, and the organic portion was separated, washed with brine, and dried. The product was purified by chromatography on silica gel, and compound was eluted with 20% ethyl acetate in hexane to give (trans)-1-Benzyl-4-isobutyl-pyrrolidine-3-carboxylic acid ethyl ester 3 as an oil (1.28 g, 44%). the bath was removed was continued overnight Saturated sodium bicarbonate was added the organic portion was separated washed with brine dried The product was purified by chromatography on silica gel, and compound was eluted with 20% ethyl acetate in hexane