methyl 5-oxopentanoate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: Under the conditions of example 1B, 470 mg of 2-bromo-6-[(1E, 3E)-(5RS)-5-hydroxy-1,3-tridecadienyl]-pyridine in 7 ml of tetrahydrofuran is mixed with 1.84 ml of n-butyllithium (1.6 molar in hexane) and 200 mg of 5-oxo-pentanoic acid methyl ester in 1.5 ml of tetrahydrofuran, worked up and chromatographed on silica gel with hexane/ethyl acetate=95/5. 29 mg of the title compound is obtained as colorless oil. chromatographed on silica gel with hexane/ethyl acetate=95/5

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

Procedure: Under the conditions of example 1B, 470 mg of 2-bromo-6-[(1E, 3E)-(5RS)-5-hydroxy-1,3-tridecadienyl]-pyridine in 7 ml of tetrahydrofuran is mixed with 1.84 ml of n-butyllithium (1.6 molar in hexane) and 200 mg of 5-oxo-pentanoic acid methyl ester in 1.5 ml of tetrahydrofuran, worked up and chromatographed on silica gel with hexane/ethyl acetate=95/5. 29 mg of the title compound is obtained as colorless oil. chromatographed on silica gel with hexane/ethyl acetate=95/5

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

Procedure: A solution of 326 mg of 2-bromo-6-[(1E)-(3RS)-3-hydroxy-1-undecenyl]-pyridine in 5 ml of tetrahydrofuran is mixed with 1.25 ml of n-butyllithium (1.6 molar in hexane) at -78° C. with stirring and under argon atmosphere. After 10 minutes, a solution of 5-oxo-pentanoic acid methyl ester in 1 ml of tetrahydrofuran is added at -78° C. and stirred for 2 hours at this temperature. The reaction mixture is mixed with water, shaken out with dichloromethane, dried on sodium sulfate, concentrated by evaporation and the crude product is chromatographed on silica gel With hexane/ethyl acetate 98/2. 188 mg of the title compound is thus obtained as colorless oil. stirred for 2 hours at this temperature dried on sodium sulfate concentrated by evaporation the crude product is chromatographed on silica gel With hexane/ethyl acetate 98/2

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

Procedure: A solution of methyl 5-oxopentanoate (1.9 g, 14.6 mmol) and (carboethoxymethylene) triphenylphosphorane (5.0 g, 14.9 mmol) in toluene (50 mL) was refluxed for 8 hours. Solvent was removed under vacuo and the crude was purified by flash chromatography on silica gel (eluant: AcOEt/hexane 2/8) to give 1.32 g (48% yield) as colorless oil of the title compound. Solvent was removed under vacuo the crude was purified by flash chromatography on silica gel (eluant: AcOEt/hexane 2/8)

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

Procedure: A solution of aldehyde (methyl 5-oxopentanoate) (1) (3.0 g, 23.1 mmol), in absolute ethanol (100 mL) is added, under stirring, to a solution of dimethyl (3S)-3-[(tert-butoxycarbonyl)amino]-2-oxo-4-phenylbutyl-phosphonate (2) (8.58 g, 23.1 mmol) and K2CO3 (3.2 g, 23.1 mmol), dried at 75° C. for 12 hours, in absolute ethanol (200 mL). The mixture is then stirred at room temperature for 16 hours, the solid residue is filtered off and the solution neutralised with glacial acetic acid. The solvent is removed under reduced pressure and the residue partitioned between ethyl acetate and a saturated solution of NaHCO3. The aqueous phase is extracted with ethyl acetate (2×50 mL) and the pooled organic phases are washed with a saturated NaCl solution and dried over anhydrous Na2SO4. The solvent is removed by distilling under reduced pressure and the product purified by means of flash chromatography on a silica gel column by using a 1:1 mixture of ethyl ether and petroleum ether as eluant. 6.8 g (79%) of a colourless oil are obtained. dried at 75° C. for 12 hours, in absolute ethanol (200 mL) the solid residue is filtered off The solvent is removed under reduced pressure the residue partitioned between ethyl acetate The aqueous phase is extracted with ethyl acetate (2×50 mL) the pooled organic phases are washed with a saturated NaCl solution dried over anhydrous Na2SO4 The solvent is removed by distilling under reduced pressure the product purified by means of flash chromatography on a silica gel column a 1:1 mixture of ethyl ether and petroleum ether as eluant

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

Procedure: A solution of methyl 5-oxopentanoate (1.9 g, 14.6 mmol) and (carboethoxymethylene) triphenylphosphorane (5.0 g, 14.9 mmol) in toluene (50 mL) was refluxed for 8 hours. Solvent was removed under vacuo and the crude was purified by flash chromatography on silica gel (eluant: AcOEt/hexane 2/8) to give 1.32 g (48% yield) as colorless oil of the title compound. Solvent was removed under vacuo the crude was purified by flash chromatography on silica gel (eluant: AcOEt/hexane 2/8)

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

Procedure: A colorless solution of commercially available methyl hex-5-enoate (5.000 g; 39.01 mmol) in dioxane (290 ml) and water (95 ml) was treated successively with 2,6-lutidine (8.360 g; 78.02 mmol), a solution of osmium tetroxide (2.5 wt. % in 2-methylpropan-2-ol; 0.50 ml), and NaIO4 (33.375 g; 156.04 mmol). The resulting beige heterogeneous reaction mixture was further stirred at rt, under nitrogen, for 16 h. The resulting milky heterogeneous mixture was treated with water (100 ml) and DCM (500 ml). The layers were separated, and the aq. layer was further extracted with DCM (200 ml/150 ml). The mixed slightly yellow organic layers were then washed with brine (200 ml), dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure to give crude methyl 5-oxopentanoate as a green oil which was directly used for the next step without additional purification. The resulting beige heterogeneous reaction mixture The layers were separated the aq. layer was further extracted with DCM (200 ml/150 ml) The mixed slightly yellow organic layers were then washed with brine (200 ml) dried over anh. MgSO4 filtered concentrated to dryness under reduced pressure

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

Procedure: To a solution of methyl 5-oxopentanoate (3.0 g, 23 mmol) in methylene chloride (75 mL) was added 2-aminopyridine (2.38 g, 25.3 mmol). The mixture was stirred at room temperature for 30 minutes. Then, the sodium triacetoxy borohydride (7.31 g, 34.5 mmol) was added and the mixture was stirred at room temperature for 4.5 hours. A saturated solution of sodium bicarbonate (40 mL) was added and the reaction mixture was extracted with ether (4×30 mL). The organic layer was washed with 0.1 N NaOH, water (2×40 mL), dried (MgSO4) and concentrated. The residue was purified by flash chromatography 1:1 (Acetone:methylene chloride) to obtain 2.31 g (48%) of the product. 1H NMR (CDCl3) 8.09-8.06 (m, 1H), 7.42-7.38 (m, 1H), 6.59-6.52 (m, 1H), 6.37 (d, J=9 Hz, 1H), 4.52 (br s, 1H), 3.68 (s, 3H), 3.29 (q, J=6 Hz, 2H), 2.40-2.31 (m, 2H), 1.8-1.61 (m, 4H). the mixture was stirred at room temperature for 4.5 hours the reaction mixture was extracted with ether (4×30 mL) The organic layer was washed with 0.1 N NaOH, water (2×40 mL) dried (MgSO4) concentrated The residue was purified by flash chromatography 1:1 (Acetone:methylene chloride)