ethyl 6-iodohexanoate

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: A suspension (100 ml) of 60% sodium hydride (2.64 g) in N,N-dimethylformamide was cooled to −18° C. with an ice-sodium chloride bath, and 31 ml of a solution of 12.62 g of 1-(p-toluoylamino)-2-propanone in N,N-dimethylformamide was added dropwise slowly. After 1-hour-stirring, 31 ml of a solution of 16.21 g of ethyl 6-iodohexanoate in N,N-dimethylformamide was added dropwise slowly. The ice-bath was removed and the mixture was stirred for 18 hours at room temperature. After addition of ice-cold water, the reaction solution was extracted with ethyl acetate, washed with water and brine sequentially, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (Wakogel® C-200, n-hexane:ethyl acetate=3:1) to provide 13.13 g of the objective compound as yellow oil. The ice-bath was removed the mixture was stirred for 18 hours at room temperature After addition of ice-cold water the reaction solution was extracted with ethyl acetate washed with water and brine sequentially dried over anhydrous magnesium sulfate the solvent was distilled off under reduced pressure The residue was purified by silica gel column chromatography (Wakogel® C-200, n-hexane:ethyl acetate=3:1)

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

Procedure: To 112 ml of a solution of 13.38 g of ethyl 6-bromohexanoate in acetone, 26.97 g of sodium iodide was added and heated to reflux for 18 hours. The reaction solution was cooled, filtered to remove insolubles and washed with acetone. The filtrate was concentrated and, after addition of water, extracted with ethyl acetate. The organic layer was washed with water and brine sequentially, dried over anhydrous magnesium sulfate and concentrated to provide 16.21 g of the objective compound as red-yellow oil. heated to reflux for 18 hours The reaction solution was cooled filtered to remove insolubles washed with acetone The filtrate was concentrated after addition of water extracted with ethyl acetate The organic layer was washed with water and brine sequentially dried over anhydrous magnesium sulfate concentrated

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

Procedure: A suspension (100 ml) of 60% sodium hydride (2.64 g) in N,N-dimethylformamide was cooled to −18° C. with an ice-sodium chloride bath, and 31 ml of a solution of 12.62 g of 1-(p-toluoylamino)-2-propanone in N,N-dimethylformamide was added dropwise slowly. After 1-hour-stirring, 31 ml of a solution of 16.21 g of ethyl 6-iodohexanoate in N,N-dimethylformamide was added dropwise slowly. The ice-bath was removed and the mixture was stirred for 18 hours at room temperature. After addition of ice-cold water, the reaction solution was extracted with ethyl acetate, washed with water and brine sequentially, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (Wakogel® C-200, n-hexane: ethyl acetate=3:1) to provide 13.13 g of the objective compound as yellow oil. The ice-bath was removed the mixture was stirred for 18 hours at room temperature After addition of ice-cold water the reaction solution was extracted with ethyl acetate washed with water and brine sequentially dried over anhydrous magnesium sulfate the solvent was distilled off under reduced pressure The residue was purified by silica gel column chromatography (Wakogel® C-200, n-hexane: ethyl acetate=3:1)

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

Procedure: A suspension (100 ml) of 60% sodium hydride (2.64 g) in N,N-dimethylformamide was cooled to −18° C. with an ice-sodium chloride bath, and 31 ml of a solution of 12.62 g of 1-(p-toluoylamino)-2-propanone in N,N-dimethylformamide was added dropwise slowly. After 1-hour-stirring, 31 ml of a solution of 16.21 g of ethyl 6-iodohexanoate in N,N-dimethylformamide was added dropwise slowly. The ice-bath was removed and the mixture was stirred for 18 hours at room temperature. After addition of ice-cold water, the reaction solution was extracted with ethyl acetate, washed with water and brine sequentially, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (Wakogel® C-200, n-hexane: ethyl acetate=3:1) to provide 13.13 g of the objective compound as yellow oil. The ice-bath was removed the mixture was stirred for 18 hours at room temperature After addition of ice-cold water the reaction solution was extracted with ethyl acetate washed with water and brine sequentially dried over anhydrous magnesium sulfate the solvent was distilled off under reduced pressure The residue was purified by silica gel column chromatography (Wakogel® C-200, n-hexane: ethyl acetate=3:1)

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

Procedure: To 112 ml of a solution of 13.38 g of ethyl 6-bromohexanoate in acetone, 26.97 g of sodium iodide was added and heated to reflux for 18 hours. The reaction solution was cooled, filtered to remove insolubles and washed with acetone. The filtrate was concentrated and, after addition of water, extracted with ethyl acetate. The organic layer was washed with water and brine sequentially, dried over anhydrous magnesium sulfate and concentrated to provide 16.21 g of the objective compound as red-yellow oil. heated to reflux for 18 hours The reaction solution was cooled filtered to remove insolubles washed with acetone The filtrate was concentrated after addition of water extracted with ethyl acetate The organic layer was washed with water and brine sequentially dried over anhydrous magnesium sulfate concentrated

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

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

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: a solution of 14 g (0.11 mol) of tetramethylthiourea and 28 g (0.10 mol) of ethyl 6-iodocaproate in 220 ml of dry acetonitrile was heated under reflux for 2 h. In a further reaction vessel 23 g (0.16 mol) of 1,8-octanediol was dissolved in 650 ml of dry acetonitrile under argon, the solution was treated with 4.5 g (0.11 mol) of a 60 percent sodium hydride suspension in mineral oil and heated under reflux for 45 min. Both batches were left to cool to 50° C. and thereupon combined cautiously within 30 min. The combined reaction mixtures were heated to reflux for 14 h., subsequently saponified with 60 ml of 10 percent potassium hydroxide solution for 3 h. at room temp., concentrated on a rotary evaporator and then added to 1 l of water. The mixture was extracted twice with 500 ml of MTBE each time, and the organic extracts were washed three times with 50 ml of 2N sodium hydroxide solution each time. The aqueous phase was acidified with conc. phosphoric acid and extracted three times with 500 ml of MTBE each time. After drying the combined organic extracts over magnesium sulphate and removing the solvent on a rotary evaporator 22 g of crude 15-hydroxy-7-thiapentadecanoic acid as a yellowish wax-like solid was obtained. An analytical sample was obtained after flash chromotography (MTBE/n-pentane, 2:1, hRf =33) on silica gel. under reflux for 2 h heated under reflux for 45 min Both batches were left The combined reaction mixtures were heated to reflux for 14 h. concentrated on a rotary evaporator added to 1 l of water The mixture was extracted twice with 500 ml of MTBE each time the organic extracts were washed three times with 50 ml of 2N sodium hydroxide solution each time extracted three times with 500 ml of MTBE each time After drying the combined organic extracts over magnesium sulphate removing the solvent on a rotary evaporator 22 g of crude 15-hydroxy-7-thiapentadecanoic acid as a yellowish wax-like solid was obtained

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

Procedure: To a solution of 2.00 g (0.0304 mole) of potassium hydroxide in 33 ml of ethanol and 5 ml of water was added 4.75 g (0.0304 mole) of 2-hydroxymethyl-3-hydroxy-6-methyl-4-pyrone, and the resulting mixture heated to 50°. A 7.8 g (0.029 mole) portion of ethyl 6-iodohexanoate was then added and the resulting clear solution heated at reflux for 7 hr under a nitrogen atmosphere. Removal of the ethanol under reduced pressure left a residue which was dissolved in methylene chloride. The organic solution was washed successively with aqueous NaHCO3 and saturated brine, was dried over magnesium sulfate, and was evaporated to afford a viscous oil. This material was chromatographed on silica gel eluting with ethyl acetate to give 5.4 g (60%) of oily product, 2-hydroxymethyl-6-methyl-3-(5-carboethoxypentyloxy)-4-pyrone. NMR (CDCl3): δ1.22 (3H, t, J = 7 Hz), 2.26 (3H, s); 4.61 (2H, m); 6.17 (1H, s). the resulting mixture heated to 50° the resulting clear solution heated at reflux for 7 hr under a nitrogen atmosphere Removal of the ethanol under reduced pressure left a residue which was dissolved in methylene chloride The organic solution was washed successively with aqueous NaHCO3 and saturated brine was dried over magnesium sulfate was evaporated to afford a viscous oil This material was chromatographed on silica gel eluting with ethyl acetate

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

Procedure: To a solution of 1.84 g (0.028 mole) of potassium hydroxide in 38 ml of ethanol and 10 ml of water was added 6.76 g (0.026 mole) of 2-hydroxymethyl-3-hydroxy-6-(trimethylacetoxymethyl)-4-pyrone, and the resulting mixture heated to 50°. An 8.3 g (0.03 mole) portion of ethyl 6-iodohexanoate was then added and the resulting clear solution heated at reflux for 7 hr under a nitrogen atmosphere. Removal of the ethanol under reduced pressure left a residue which was dissolved in methylene chloride. The organic solution was washed successively with aqueous NaHCO3 and saturated brine, was dried over magnesium sulfate, and was evaporated to afford a viscous oil. This material was chromatographed on silica gel eluting with ethyl acetate to give 2.9 g (27%) of oily product, 2-hydroxy-3-(5-carboethoxypentyloxy)-6-(trimethylacetoxymethyl)-4-pyrone. NMR (CDCl3): δ1.22 (3H, t, J = 7 Hz), 1.23 (9H, s), 2.30 (2H, t, J = 5.5 Hz), 6.32 (1H, s). the resulting mixture heated to 50° the resulting clear solution heated at reflux for 7 hr under a nitrogen atmosphere Removal of the ethanol under reduced pressure left a residue which was dissolved in methylene chloride The organic solution was washed successively with aqueous NaHCO3 and saturated brine was dried over magnesium sulfate was evaporated to afford a viscous oil This material was chromatographed on silica gel eluting with ethyl acetate