1-bromohexadecane

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:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2,4,6-Trihydroxybenzaldehyde (435 mg, 2.53 mmol), 1-bromohexadecane (4.58 g, 15.0 mmol), K2CO3 (1.04 g, 4.52 mmol) and KI (70 mg, 0.42 mmol) were mixed in DMF (15 ml), followed by stirring at 70° C. for 20 hours. The resulting reaction product was cooled to 20° C., and chloroform (100 ml) was added thereto to separate into an organic phase and an aqueous phase. The subsequent operations are the same as in Example 1, and therefore are omitted to describe. Thus, white solid 2,4,6-trihexadecyloxybenzaldehyde (2a) was obtained (1.04 g, yield: 50%). It was confirmed by 1H NMR quantitative analysis that 2a is 2,4,6-trihexadecyloxybenzaldehyde. The resulting reaction product was cooled to 20° C. to separate into an organic phase

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 0.27 g of a 55% w/w suspension of sodium hydride in mineral oil was suspended in 2 ml of dimethylformamide. To the suspension was added dropwise a solution of 1.210 g of dl-cis-2-benzyloxymethyl-3-mercaptotetrahydropyran (prepared as described in Preparation 16) in 5 ml of dimethylformamide, whilst ice-cooling the mixture. The reaction mixture was stirred at 60° C. for 1 hour, after which it was cooled to room temperature. A solution of 1.86 g of hexadecyl bromide in 3 ml of dimethylformamide was then added, and the mixture was stirred at room temperature for 1 hour. It was then poured into water and extracted with ethyl acetate. The extract was washed with water, dried and concentrated by evaporation under reduced pressure. The resulting residue was subjected to column chromatography through 40 g of silica gel. The fraction eluted with mixtures of diethyl ether and hexane ranging from 3:97 to 10:90 by volume was collected to give 2.284 g of the title compound as a solid. whilst ice-cooling the mixture after which it was cooled to room temperature the mixture was stirred at room temperature for 1 hour extracted with ethyl acetate The extract was washed with water dried concentrated by evaporation under reduced pressure The fraction eluted with mixtures of diethyl ether and hexane ranging from 3:97 to 10:90 by volume was collected

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

Procedure: A solution of 4.09 g of 4,5-dihydrofurfuryl alcohol (prepared as described in Preparation 12) in 10 ml of dimethylformamide was added dropwise to 2.62 g of a 55% w/w suspension of sodium hydride in mineral oil, itself suspended in 40 ml of dimethylformamide, whilst maintaining the temperature of the mixture at from 5° to 12° C. by ice-cooling. The mixture was then stirred at room temperature for 30 minutes, 18.32 g of hexadecyl bromide were added to the solution, and the whole was stirred at room temperature for 15 hours. The reaction mixture was then poured into 200 ml of water, and extracted twice with diethyl ether. The extract was washed with water, dried and condensed by evaporation under reduced pressure. The oily residue, 17 g, was subjected to column chromatography through 400 g of Grade II-III alumina (a product of Woelm Pharma, West Germany). The fraction eluted with a 1:20 by volume mixture of diethyl ether and hexane gave 9.512 g of the title compound as a solid, melting at 30.5°-31.5° C. (cold hexane). whilst maintaining the temperature of the mixture at from 5° to 12° C. by ice- cooling the whole was stirred at room temperature for 15 hours extracted twice with diethyl ether The extract was washed with water dried condensed by evaporation under reduced pressure The fraction eluted with a 1:20 by volume mixture of diethyl ether and hexane

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1.037 g of dl-cis-2-benzyloxymethyl-3-hydroxytetrahydropyran (prepared as described in Preparation 9), 1.709 g of hexadecyl bromide, 0.77 g of potassium hydroxide and 15 ml of toluene was heated, with stirring, at 120° C. for 10 hours. The reaction mixture was cooled and then poured into water. The water layer was extracted twice with diethyl ether. The organic layer and the extracts were combined, washed with water, dried and condensed by evaporation under reduced pressure. The resulting oily residue, 3.3 g, was subjected to column chromatography through 50 g of silica gel. The fraction eluted with a 1:10 by volume mixture of diethyl ether and hexane gave 1.455 g of the title compound as a colorless oily substance. was heated The reaction mixture was cooled The water layer was extracted twice with diethyl ether washed with water dried condensed by evaporation under reduced pressure The fraction eluted with a 1:10 by volume mixture of diethyl ether and hexane

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

Procedure: A solution of 2.22 g of dl-trans-2-benzyloxymethyl-3-hydroxytetrahydropyran (prepared as described in Preparation 6) in 10 ml of dimethylformamide was added dropwise, with ice-cooling, to 10 ml of dimethylformamide containing suspended in it 0.480 g of a 55% w/w suspension of sodium hydride in mineral oil. The reaction mixture was stirred at room temperature for 60 minutes, after which 5.49 g of hexadecyl bromide were added, and the resulting mixture was stirred for a further 4 hours. Finally, the mixture was stirred at 60° C. for 60 minutes and then cooled. It was then poured into 100 ml of water, and extracted twice with ethyl acetate. The extract was washed with water, dried and condensed by evaporation under reduced pressure. The oily residue was subjected to column chromatography resulting through 100 g of silica gel. The fraction eluted with mixtures of diethyl ether and hexane ranging from 1:20 to 1:10 by volume gave 3.82 g of the title compound as a solid having a low melting point, melting at 28.5°-29.5° C. (cold methanol). the resulting mixture was stirred for a further 4 hours Finally, the mixture was stirred at 60° C. for 60 minutes cooled extracted twice with ethyl acetate The extract was washed with water dried condensed by evaporation under reduced pressure resulting through 100 g of silica gel The fraction eluted with mixtures of diethyl ether and hexane ranging from 1:20 to 1:10 by volume

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

Procedure: 5.71 g of 6-hydroxymethyl-3,4-dihydro-2H-pyran, 16.79 g of hexadecyl bromide and 8.22 g of pulverized 85% potassium hydroxide were mixed in 160 ml of toluene and heated under reflux for 2 hours. The mixtured was then cooled, washed with water, dried and condensed by evaporation under reduced pressure. The resulting oily residue, 17 g, was subjected to column chromatography through 400 g of silica gel. The fraction eluted with a 1:5 by volume mixture of diethyl ether and hexane gave 14.38 g of the title compound as a colorless oily substance. heated under reflux for 2 hours The mixtured was then cooled washed with water dried condensed by evaporation under reduced pressure The fraction eluted with a 1:5 by volume mixture of diethyl ether and hexane

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

Procedure: (R)-(−)-2,2-dimethyl-1,3-dioxolane-4-methanol (11 grams), powdered potassium hydroxide (20 grams) and hexadecyl bromide (27.96 grams) in toluene (150 ml) were stirred and refluxed for 6 hours, while removing the water formed by azeotropic distillation. The volume of the solvent was gradually reduced to about 40 ml. The reaction mixture was cooled to room temperature; water was added (100 ml) and the resulting mixture was extracted with dichloromethane (3×75 ml). The combined organic phase was washed with water (50 ml) and the solvent removed under reduced pressure. The residue was dissolved in 200 ml mixture of 90:10:5 methanol:water:concentrated hydrochloric acid (v/v) and the resulting solution was refluxed for 2 hours, followed by cooling to room temperature and addition of water (100 ml). The product was extracted with dichloromethane (3×100 ml), and the organic phase was washed consecutively with water (100 ml). saturated aqueous solution of sodxium carbonate (100 ml) and again with water (100 ml). The solvent was removed under reduced pressure and the product was crystallized from hexane (200 ml) to give 21.69 grams (yield 82%) of pure 1-hexadecyl-glycerol. upon drying in a desiccator under reduced pressure. refluxed for 6 hours while removing the water formed by azeotropic distillation the resulting mixture was extracted with dichloromethane (3×75 ml) The combined organic phase was washed with water (50 ml) the solvent removed under reduced pressure The residue was dissolved in 200 ml mixture of 90:10:5 methanol water:concentrated hydrochloric acid (v/v) and the resulting solution was refluxed for 2 hours by cooling to room temperature addition of water (100 ml) The product was extracted with dichloromethane (3×100 ml) the organic phase was washed consecutively with water (100 ml) The solvent was removed under reduced pressure the product was crystallized from hexane (200 ml)

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

Procedure: 1-Hexadecyl-3-tritylglycerol was prepared as described in U.S. Pat. No. 6,838,452. In brief, D-acetone glycerol (4 grams), powdered potassium hydroxide (approximately 10 grams) and hexadecyl bromide (9.3 grams) in benzene (100 ml) were stirred and refluxed for 5 hours, while removing the water formed by azeotropic distillation (compare W. J. Baumann and H. K. Mangold, J. Org. Chem. 29: 3055, 1964 and F. Paltauf, Monatsh. 99:1277, 1968). The volume of the solvent was gradually reduced to about 20 ml, and the resulting mixture was cooled to room temperature and dissolved in ether (100 ml). The resulting solution was washed with water (2×50 ml), and the solvent was removed under reduced pressure. A 100 ml mixture of 90:10:5 methanol:water:concentrated hydrochloric acid was added to the residue and the mixture was refluxed for 10 minutes. The product was extracted with ether (200 ml) and was washed consecutively with water (50 ml), 10% sodium hydroxide (20 ml) and again with water (volumes of 20 ml) until neutral. The solvent was removed under reduced pressure and the product (8.8 grams) was crystallized from hexane to give 7.4 grams of pure 1-hexadecyl-glycerol. refluxed for 5 hours while removing the water formed by azeotropic distillation (compare W. J. Baumann and H. K. Mangold, J. Org. Chem. 29: 3055, 1964 and F. Paltauf, Monatsh. 99:1277, 1968) The resulting solution was washed with water (2×50 ml) the solvent was removed under reduced pressure A 100 ml mixture of 90:10:5 methanol:water:concentrated hydrochloric acid was added to the residue the mixture was refluxed for 10 minutes The product was extracted with ether (200 ml) was washed consecutively with water (50 ml), 10% sodium hydroxide (20 ml) and again with water (volumes of 20 ml) until neutral The solvent was removed under reduced pressure the product (8.8 grams) was crystallized from hexane