methyl 15-hydroxypentadecanoate

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

Procedure: To a solution of methyl 15-hydroxypentadecanoate (4.2 g, 15.6 mmol, 1.0 eq) and carbon tetrabromide (5.7 g, 17.1 mmol, 1.1 eq) in dichloromethane (15 mL) cooled to 0° C., was added triphenyl phosphine (4.3 g, 17.1 mmol, 1.1 eq) in portions over 30 min with vigorous stirring. Upon addition of the phosphine, the colourless solution turned a pale brown colour and was stirred for an additional 2 hours at room temperature. The mixture was concentrated in vacuo (using a rotary evaporator attached to a diaphragm pump) to a brown oil. Hexane (200 mL) was quickly added and the resulting mixture was stirred for 15 minutes. The resultant white precipitate was removed by filtration, and the filtrate was concentrated in vacuo. The product was purified by silica gel chromatography (20:1 hexane:ethyl acetate), yielding methyl 15-bromopentadecanoate (4.6 g, 90%) as a colourless solid. The mixture was concentrated in vacuo ( a rotary evaporator Hexane (200 mL) was quickly added the resulting mixture was stirred for 15 minutes The resultant white precipitate was removed by filtration the filtrate was concentrated in vacuo The product was purified by silica gel chromatography (20:1 hexane:ethyl acetate)

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

Procedure: To a solution of methyl 15-hydroxypentadecanoate (4.2 g, 15.6 mmol, 1.0 eq) and carbon tetrabromide (5.7 g, 17.1 mmol, 1.1 eq) in dichloromethane (15 mL) cooled to 0° C., was added triphenyl phosphine (4.3 g, 17.1 mmol, 1.1 eq) in portions over 30 min with vigorous stirring. Upon addition of the phosphine, the colourless solution turned a pale brown colour and was stirred for an additional 2 hours at room temperature. The mixture was concentrated in vacuo (using a rotary evaporator attached to a diaphragm pump) to a brown oil. Hexane (200 mL) was quickly added and the resulting mixture was stirred for 15 minutes. The resultant white precipitate was removed by filtration, and the filtrate was concentrated in vacuo. The product was purified by silica gel chromatography (20:1 hexane:ethyl acetate), yielding methyl 15-bromopentadecanoate (4.6 g, 90%) as a colourless solid. The mixture was concentrated in vacuo ( a rotary evaporator Hexane (200 mL) was quickly added the resulting mixture was stirred for 15 minutes The resultant white precipitate was removed by filtration the filtrate was concentrated in vacuo The product was purified by silica gel chromatography (20:1 hexane:ethyl acetate)

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

Procedure: Sodium methoxide was generated by the addition of sodium metal (2.4 g, 104.3 mmol, 5.0 eq) to methanol (130 mL) at 0° C. with stirring. The mixture was warmed to room temperature and stirred until all of the sodium was consumed. ω-Pentadecalactone (5.0 g, 20.8 mmol, 1.0 eq) was added in a single portion, and the solution was stirred at 80° C. for 3 hours. The reaction was quenched with hydrochloric acid (1 M, 175 mL) and diluted with water (175 mL). The aqueous layer was extracted with ether (3×100 mL), and the combined organic layers were washed with water (150 mL), brine (150 mL), and dried over magnesium sulphate. The product was purified by silica gel chromatography (2:1 hexane:ethyl acetate), yielding methyl 15-hydroxypentadecanoate (4.24 g, 85%) as a colourless solid. was consumed the solution was stirred at 80° C. for 3 hours The reaction was quenched with hydrochloric acid (1 M, 175 mL) diluted with water (175 mL) The aqueous layer was extracted with ether (3×100 mL) the combined organic layers were washed with water (150 mL), brine (150 mL) dried over magnesium sulphate The product was purified by silica gel chromatography (2:1 hexane:ethyl acetate)

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

Procedure: 150 g (499 mmol) of dimethyl 1,15-pentadecandioate and 750 mg (0.5% by weight per the diester) of a commercial copper-chromium catalyst (content of copper as copper oxides: 42% by weight) were added to an autoclave and subjected to hydrogenation reaction at the hydrogen pressure of 20.0 Mpa at 280° C. After 2 hours, methyl 15-hydroxypentadecanoate was obtained in 35% yield. The degree of the conversion was 67% the selectivity was 53%, and the yield was 35%.

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

Procedure: 150 g (499 mmol) of dimethyl 1,15-pentadecandioate and 12 g (8.0% by weight per the diester) of the catalyst prepared in Preparative Example 1 were added to an autoclave and subjected to hydrogenation reaction at the hydrogen pressure of 20.0 Mpa at 250° C. After 8 hours, the degree of the conversion was 63% and the selectivity was 87%. The reaction was further continued, and after 10 hours, methyl 15-hydroxypentadecanoate was obtained in 61% yield. The results are shown in Table 2. were added to an autoclave after 10 hours

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

Procedure: 150 g (499 mmol) of dimethyl 1,15-pentadecandioate and 12 g (8.0% by weight per the diester) of the catalyst prepared in Preparative Example 1 were added to an autoclave and subjected to hydrogenation reaction at the hydrogen pressure of 20.0 Mpa at 250° C. After 8 hours, the degree of the conversion was 63% and the selectivity was 87%. The reaction was further continued, and after 10 hours, methyl 15-hydroxypentadecanoate was obtained in 61% yield. The results are shown in Table 2. were added to an autoclave after 10 hours

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

Procedure: A 13.1 g (48.1 mmol) portion of methyl 15-hydroxypentadecanoate, 45.1 g (100 mmol) of polyoxyethylene lauryl ether {average addition mol number 6} and 1.0 g of magnesium oxide were put into the same apparatus of Inventive Example 1, and the reaction was carried out under ambient pressure to 1.3 kPa and at 190 to 245° C. for 3 hours, while distilling out methanol, and then under 53 Pa and at 160 to 260° C. to obtain 19.5 g of a colorless to light yellow liquid. This distillate contained 11.0 g of cyclopentadecanolide (yield 95%). while distilling out methanol under 53 Pa and at 160 to 260° C. to obtain 19.5 g of a colorless to light yellow liquid

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

Procedure: To a solution of methyl 15-hydroxypentadecanoate (4.2 g, 15.6 mmol, 1.0 eq) and carbon tetrabromide (5.7 g, 17.1 mmol, 1.1 eq) in dichloromethane (15 mL) cooled to 0° C., was added triphenyl phosphine (4.3 g, 17.1 mmol, 1.1 eq) in portions over 30 min with vigorous stirring. Upon addition of the phosphine, the colourless solution turned a pale brown colour and was stirred for an additional 2 hours at room temperature. The mixture was concentrated in vacuo (using a rotary evaporator attached to a diaphragm pump) to a brown oil. Hexane (200 mL) was quickly added and the resulting mixture was stirred for 15 minutes. The resultant white precipitate was removed by filtration, and the filtrate was concentrated in vacuo. The product was purified by silica gel chromatography (20:1 hexane:ethyl acetate), yielding methyl 15-bromopentadecanoate (4.6 g, 90%) as a colourless solid. The mixture was concentrated in vacuo ( a rotary evaporator Hexane (200 mL) was quickly added the resulting mixture was stirred for 15 minutes The resultant white precipitate was removed by filtration the filtrate was concentrated in vacuo The product was purified by silica gel chromatography (20:1 hexane:ethyl acetate)

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

Procedure: Sodium methoxide was generated by the addition of sodium metal (2.4 g, 104.3 mmol, 5.0 eq) to methanol (130 mL) at 0° C. with stirring. The mixture was warmed to room temperature and stirred until all of the sodium was consumed. ω-Pentadecalactone (5.0 g, 20.8 mmol, 1.0 eq) was added in a single portion, and the solution was stirred at 80° C. for 3 hours. The reaction was quenched with hydrochloric acid (1 M, 175 mL) and diluted with water (175 mL). The aqueous layer was extracted with ether (3×100 mL), and the combined organic layers were washed with water (150 mL), brine (150 mL), and dried over magnesium sulphate. The product was purified by silica gel chromatography (2:1 hexane:ethyl acetate), yielding methyl 15-hydroxypentadecanoate (4.24 g, 85%) as a colourless solid. was consumed the solution was stirred at 80° C. for 3 hours The reaction was quenched with hydrochloric acid (1 M, 175 mL) diluted with water (175 mL) The aqueous layer was extracted with ether (3×100 mL) the combined organic layers were washed with water (150 mL), brine (150 mL) dried over magnesium sulphate The product was purified by silica gel chromatography (2:1 hexane:ethyl acetate)