ethyl 5-iodopentanoate

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: Following the procedure of Example 12 except substituting 1-heptenylcarboxylic acid for 1-decenylcarboxylic acid, and ethyl-5 iodovalerate for ethyl-4-iodobutyrate and eliminating the addition of dicyclohexylamine, the title compound is obtained.

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

Procedure: NaH (0.4 g, 8.4 mmol) was washed with hexanes and then suspended in dry THF (55 mL). 5-Ethylthiopentanethiol (8 mmol, 73% pure by GC analysis, contaminated by 1,5-bis(ethylthio)pentane, 1.80 g of mixture) in THF (8 mL) was added and stirred for 1 h at room temperature. Ethyl 5-iodovalerate (2.1 g, 8 mmol) in THF (8 mL) was added and the mixture refluxed for 8 h. The solvent was evaporated in vacuo, the residue was dissolved in EtOAc (150 mL), washed with water (2 ×50 mL), brine (50 mL), dried (Na2SO4), chromatographed (silica gel, EtOAc/hexanes 1:10) and distilled (Kugelrohr) to yield the title compound (1.86 g, 80%) as a colorless oil (bp 147° C.-149° C./0.2 torr). IR (neat): 1740 cm-1. 1H-NMR: 1.25 (t, 6H); 1.50 (quintet, 2H); 1.54- 1.67 (m, 6H); 1.73 quintet, 2H); 2.32 (t, 2H); 2.46-2.57 (m, 8H); and 4.12 (q, 2H). Anal. Calcd for C14H28S2O2 : C, 57.49; H, 9.65%. Found: C, 57.36; H, 9.59%. the mixture refluxed for 8 h The solvent was evaporated in vacuo the residue was dissolved in EtOAc (150 mL) washed with water (2 ×50 mL), brine (50 mL) dried (Na2SO4) chromatographed (silica gel, EtOAc/hexanes 1:10) distilled (Kugelrohr)

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

Procedure: NaH (0.4 g, 8.4 mmol) was washed with hexanes and then suspended in dry THF (55 mL). 5-Ethylthiopentanethiol (8 mmol, 73% pure by GC analysis, contaminated by 1,5-bis(ethylthio)pentane, 1.80 g of mixture) in THF (8 mL) was added and stirred for 1 h at room temperature. Ethyl 5-iodovalerate (2.1 g, 8 mmol) in THF (8 mL) was added and the mixture refluxed for 8 h. The solvent was evaporated in vacuo, the residue was dissolved in EtOAc (150 mL), washed with water (2 ×50 mL), brine (50 mL), dried (Na2SO4), chromatographed (silica gel, EtOAc/hexanes 1:10) and distilled (Kugelrohr) to yield the title compound (1.86 g, 80%) as a colorless oil (bp 147° C.-149° C./0.2 torr). IR (neat): 1740 cm-1. 1H-NMR: 1.25 (t, 6H); 1.50 (quintet, 2H); 1.54- 1.67 (m, 6H); 1.73 quintet, 2H); 2.32 (t, 2H); 2.46-2.57 (m, 8H); and 4.12 (q, 2H). Anal. Calcd for C14H28S2O2 : C, 57.49; H, 9.65%. Found: C, 57.36; H, 9.59%. the mixture refluxed for 8 h The solvent was evaporated in vacuo the residue was dissolved in EtOAc (150 mL) washed with water (2 ×50 mL), brine (50 mL) dried (Na2SO4) chromatographed (silica gel, EtOAc/hexanes 1:10) distilled (Kugelrohr)

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

Procedure: To illustrate the preparation of the dithia-substituted fatty acid ethers, 5-ethylthiopentane thiol can be reacted with sodium hydride and the resulting product reacted with ethyl 5-iodovalerate to yield ethyl 6,12-dithiatetradecanoate. The ester group can then be removed by treatment with alkali metal hydroxide, e.g. NaOH, to produce the desired 6,12-dithiatetradecanoic acid.

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

Procedure: To illustrate the preparation of the dithia-substituted fatty acid ethers, 5-ethylthiopentane thiol can be reacted with sodium hydride and the resulting product reacted with ethyl 5-iodovalerate to yield ethyl 6,12-dithiatetradecanoate. The ester group can then be removed by treatment with alkali metal hydroxide, e.g. NaOH, to produce the desired 6,12-dithiatetradecanoic acid.

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

Procedure: To a suspension of tert-butyl 4-methoxy-3-oxobutanoate (3.09 g) and potassium carbonate (2.50 g) in dimethylformamide (20 mL) was added ethyl 5-iodopentanoate (4.62 g) and the mixture was stirred at ambient temperature for 15 hours. The mixture was partitioned between ethyl acetate and water. The organic layer was separated, washed with water and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by silica gel column chromatography eluting with a mixture of hexane and ethyl acetate (20:1-5:1) to give 1-tert-butyl 7-ethyl 2-(methoxyacetyl)heptanedioate as colorless oil (4.33 g). The mixture was partitioned between ethyl acetate and water The organic layer was separated washed with water and brine dried over magnesium sulfate evaporated in vacuo The residue was purified by silica gel column chromatography eluting with a mixture of hexane and ethyl acetate (20:1-5:1)

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

Procedure: To a suspension of tert-butyl 4-methoxy-3-oxobutanoate (3.09 g) and potassium carbonate (2.50 g) in dimethylformamide (20 mL) was added ethyl 5-iodopentanoate (4.62 g) and the mixture was stirred at ambient temperature for 15 hours. The mixture was partitioned between ethyl acetate and water. The organic layer was separated, washed with water and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by silica gel column chromatography eluting with a mixture of hexane and ethyl acetate (20:1-5:1) to give 1-tert-butyl 7-ethyl 2-(methoxyacetyl)heptanedioate as colorless oil (4.33 g). The mixture was partitioned between ethyl acetate and water The organic layer was separated washed with water and brine dried over magnesium sulfate evaporated in vacuo The residue was purified by silica gel column chromatography eluting with a mixture of hexane and ethyl acetate (20:1-5:1)

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

Procedure: To a solution of tert-butyl 4-(methylthio)-3-oxobutanoate (5.00 g) and potassium carbonate (3.72 g) in dimethylformamide (25 mL) was added ethyl 5-iodopentanoate (6.89 g) and the mixture was stirred at ambient temperature for 15 hours. The mixture was partitioned between ethyl acetate and water. The organic layer was separated, washed with water and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by silica gel column chromatography eluting with a mixture of hexane and ethyl acetate (20:1-10:1) to give 1-tert-butyl 7-ethyl 2-[(methylthio)acetyl]heptanedioate as colorless oil (5.88 g). The mixture was partitioned between ethyl acetate and water The organic layer was separated washed with water and brine dried over magnesium sulfate evaporated in vacuo The residue was purified by silica gel column chromatography eluting with a mixture of hexane and ethyl acetate (20:1-10:1)

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

Procedure: To a solution of tert-butyl 3-oxobutanoate (20.0 g) in tetrahydrofuran (200 mL) was added 60% sodium hydride in oil (5.56 g) portionwise over 20 minutes in an ice-water bath under N2. After 40 minutes, to the mixture was added ethyl 5-iodopentanoate (35.6 g) at the temperature. After 15 minutes, the mixture was stirred at ambient temperature. After 1 hour, the reaction mixture was heated at 50° C. for 24 hours. The cooled mixture was partitined between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with water and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by flash silica gel chromatography (silica gel, 1 L) eluting with hexane-ethyl acetate=50-1, 20-1, 10-1, and 8-1 to give 1-tert-butyl 7-ethyl 2-acetylheptanedioate (27.3 g, 75.4%) as colorless oil. After 15 minutes After 1 hour the reaction mixture was heated at 50° C. for 24 hours The aqueous layer was extracted with ethyl acetate The combined organic layer was washed with water and brine dried over magnesium sulfate evaporated in vacuo The residue was purified by flash silica gel chromatography (silica gel, 1 L) eluting with hexane-ethyl acetate=50-1, 20-1, 10-1, and 8-1

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

Procedure: Following the procedure of Example 12 except substituting 1-heptenylcarboxylic acid for 1-decenylcarboxylic acid, and ethyl-5 iodovalerate for ethyl-4-iodobutyrate and eliminating the addition of dicyclohexylamine, the title compound is obtained.