dodecan-2-ol

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A reaction vessel of glass, 3000 ml in inner volume, provided with stirring vanes and a reflux condenser was charged with 810 g (4.82 mols) of 1-dodecene, 900 g (14.52 mols) of monoethylene glycol, and 100 g of the BEA type zeolite (produced by PQ Corp. and marketed under trademark designation of "VALFOR CP 811 BL-25"). The vapor-phase part of the reaction vessel was displaced with nitrogen and then retained in the atmosphere of nitrogen at normal pressure. The reaction mixture was heated to and kept at 150° C. for three hours and meanwhile kept stirred at 600 rpm to induce reaction. The reaction solution was cooled to room temperature. The dodecene phase in the upper layer was separated and distilled to expel the unaltered dodecene. The residue of the distillation was treated under a reduced pressure of 2 mmHg in a boiling point range of 129° to 131° C. to obtain 255 g of a secondary dodecanol ethoxylate composition. A reaction vessel of glass, 3000 ml in inner volume, provided with stirring vanes and a reflux condenser The reaction mixture was heated to and reaction The dodecene phase in the upper layer was separated distilled The residue of the distillation was treated under a reduced pressure of 2 mmHg in a boiling point range of 129° to 131° C.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A reaction vessel of glass, 3000 ml in inner volume, provided with stirring vanes and a reflux condenser was charged with 810 g (4.82 mols) of a dodecene-isomer mixture (composed of 25 mol % of 1-dodecene and 75 mol % of inner dodecene) obtained by causing 1-dodecene to react in the liquid phase with 5% by weight of a BEA type zeolite (produced by PQ Corp. and marketed under trademark designation of "VALFOR CP 811 BL-25") at 150° C. for 10 hours, 900 g (14.52 mols) of monoethylene glycol, and 100 g of the BEA type zeolite (produced by PQ Corp. and marketed under trademark designation of "VALFOR CP 811 BL-25"). The vapor-phase part of the reaction vessel was displaced with nitrogen and then retained in the atmosphere of nitrogen at normal pressure. The reaction mixture was heated to and kept at 150° C. for three hours and meanwhile kept stirred at 600 rpm to induce reaction. The reaction solution was cooled to room temperature. The dodecene phase in the upper layer was separated and distilled to expel the unaltered dodecene. The residue of the distillation was treated under a reduced pressure of 2 mmHg in a boiling point range of 129° to 131° C., to obtain 155 g of a secondary dodecanol ethoxylate composition. A reaction vessel of glass, 3000 ml in inner volume, provided with stirring vanes and a reflux condenser obtained The reaction mixture was heated to and reaction The dodecene phase in the upper layer was separated distilled The residue of the distillation was treated under a reduced pressure of 2 mmHg in a boiling point range of 129° to 131° C.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The procedure is the same as for preparing n-dodecyl chloroformate except freshly distilled 2-dodecanol (41.3 g, 0.222 moles) is added to the phosgene mixture. 99% yields of 2-dodecyl chloroformate are obtained. The product is purified via distillation (90° C. at 0.1 mm Hg). 1H MNR (60 MHz, neat) δ 4.6-4.98 (1H,m), δ 1.5-1.8 (21H,m), δ0.89 (3H, t). IR (neat) 1780 cm-1 (carbonyl).

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: When in the procedure of Example 13 (c) an appropriate amount of the mesylate of 2-dodecanol was substituted for 1-bromododecane and the general procedures for Example 13 (c), (d), and (e) were followed, E-N-(2,6-diisopropylphenyl)-2-(2-(1-methylundecyl) -2H-tetrazol-5-yl)-2-methoxyimino-acetamide was obtained;

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: When in the procedure of Example 13 (c) an appropriate amount of the mesylate of 2-dodecanol was substituted for 1-bromododecane and the general procedures for Example 13 (c), (d), and (e) were followed, E-N-(2,6-diisopropylphenyl)-2-(2-(1-methylundecyl) -2H-tetrazol-5-yl)-2-methoxyimino-acetamide was obtained;

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: When in the procedure of Example 13 (c) an appropriate amount of the mesylate of 2-dodecanol was substituted for 1-bromododecane and the general procedures for Example 13 (c), (d), and (e) were followed, E-N-(2,6-diisopropylphenyl)-2-(2-(1-methylundecyl) -2H-tetrazol-5-yl)-2-methoxyimino-acetamide was obtained;

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 250 mL three neck round bottom flask was equipped with an overhead stirrer, thermocouple, temperature controller and nitrogen sweep then charged with 10.0 g (25.34 mmol) of bendamustine hydrochloride, 4.77 g (5.75 mL, 25.6 mmol, 1.01 eq) of 2-dodecanol, 5.3 g (25.6 mmol, 1.01 eq) of dicyclohexylcarbodiimide (DCC), 100 mL of MDC and 0.31 g (2.54 mmol, 0.1 eq) of DMAP. The reaction was stirred at room temperature overnight at which time an in process analysis indicated the reaction was complete. Solids were removed by vacuum filtration and washed with 25 mL of MDC. The filtrate was diluted with 200 mL of MDC then washed with 4% aqueous sodium bicarbonate solution (1×500 mL) before drying over sodium sulfate, filtering and concentrating to dryness in vacuo to an off-white solid. This solid was triturated with 25 mL of MDC and the solid impurities were removed by vacuum filtration and washed with 5 mL of MDC. The filtrate was concentrated to dryness in vacuo to yield the crude product which was shown to contain residual 2-dodecanol by 1H NMR. The crude product was chromatographed using 100 g of silica gel 60, 230-400 mesh, eluting with first 1 L of heptanes, then 500 mL of 3:1 heptane/EtOAc, 500 of 2:1 heptane/EtOAc and finally 500 mL of 1:1 heptane/EtOAc collecting 100 mL fractions. Product containing fractions were combined and concentrated to dryness in vacuo to yield 5.35 g (10.16 mmol, 40%) of the product as a light purple viscous oil with an HPLC purity of 99.5 A %. 1HNMR (400 MHz, DMSO-d6) δ 7.31 (d, J=8.76 Hz, 1H), 6.93 (d, J=2.28 Hz, 1H), 6.78 (dd, J=2.36, 8.76 Hz, 1H), 4.8 (m, 1H), 3.7 (s, 8H), 3.65 (s, 3H), 2.82 (t, J=7.4 Hz, 2H), 2.42 (t, J=7.36 Hz, 2H), 2.00 (m, 2H), 1.50 (m, 2H), 1.25 (s, b, 16H), 1.14 (d, J=6.24, 2H), 0.84 (t, J=6.68 Hz, 3H). Solids were removed by vacuum filtration washed with 25 mL of MDC The filtrate was diluted with 200 mL of MDC then washed with 4% aqueous sodium bicarbonate solution (1×500 mL) before drying over sodium sulfate filtering concentrating to dryness in vacuo to an off-white solid This solid was triturated with 25 mL of MDC the solid impurities were removed by vacuum filtration washed with 5 mL of MDC The filtrate was concentrated to dryness in vacuo to yield the crude product which The crude product was chromatographed eluting with first 1 L of heptanes Product containing fractions concentrated to dryness in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 250 mL three neck round bottom flask was equipped with an overhead stirrer, thermocouple, temperature controller and nitrogen sweep then charged with 10.0 g (25.34 mmol) of bendamustine hydrochloride, 4.77 g (5.75 mL, 25.6 mmol, 1.01 eq) of 2-dodecanol, 5.3 g (25.6 mmol, 1.01 eq) of dicyclohexylcarbodiimide (DCC), 100 mL of MDC and 0.31 g (2.54 mmol, 0.1 eq) of DMAP. The reaction was stirred at room temperature overnight at which time an in process analysis indicated the reaction was complete. Solids were removed by vacuum filtration and washed with 25 mL of MDC. The filtrate was diluted with 200 mL of MDC then washed with 4% aqueous sodium bicarbonate solution (1×500 mL) before drying over sodium sulfate, filtering and concentrating to dryness in vacuo to an off-white solid. This solid was triturated with 25 mL of MDC and the solid impurities were removed by vacuum filtration and washed with 5 mL of MDC. The filtrate was concentrated to dryness in vacuo to yield the crude product which was shown to contain residual 2-dodecanol by 1H NMR. The crude product was chromatographed using 100 g of silica gel 60, 230-400 mesh, eluting with first 1 L of heptanes, then 500 mL of 3:1 heptane/EtOAc, 500 of 2:1 heptane/EtOAc and finally 500 mL of 1:1 heptane/EtOAc collecting 100 mL fractions. Product containing fractions were combined and concentrated to dryness in vacuo to yield 5.35 g (10.16 mmol, 40%) of the product as a light purple viscous oil with an HPLC purity of 99.5A %. 1H NMR (400 MHz, DMSO-d6) δ 7.31 (d, J=8.76 Hz, 1H), 6.93 (d, J=2.28 Hz, 1H), 6.78 (dd, J=2.36, 8.76 Hz, 1H), 4.8 (m, 1H), 3.7 (s, 8H), 3.65 (s, 3H), 2.82 (t, J=7.4 Hz, 2H), 2.42 (t, J=7.36 Hz, 2H), 2.00 (m, 2H), 1.50 (m, 2H), 1.25 (s, b, 16H), 1.14 (d, J=6.24, 2H), 0.84 (t, J=6.68 Hz, 3H). Solids were removed by vacuum filtration washed with 25 mL of MDC The filtrate was diluted with 200 mL of MDC then washed with 4% aqueous sodium bicarbonate solution (1×500 mL) before drying over sodium sulfate filtering concentrating to dryness in vacuo to an off-white solid This solid was triturated with 25 mL of MDC the solid impurities were removed by vacuum filtration washed with 5 mL of MDC The filtrate was concentrated to dryness in vacuo to yield the crude product which The crude product was chromatographed eluting with first 1 L of heptanes Product containing fractions concentrated to dryness in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A reaction vessel of glass, 3000 ml in inner volume, provided with stirring vanes and a reflux condenser was charged with 810 g (4.82 mols) of 1-dodecene, 900 g (14.52 mols) of monoethylene glycol, and 100 g of the BEA type zeolite (produced by PQ Corp. and marketed under trademark designation of “VALFOR CP 811 BL-25”). The vapor-phase part of the reaction vessel was displaced with nitrogen and then retained in the atmosphere of nitrogen at normal pressure. The reaction mixture was heated to and kept at 150° C. for three hours and meanwhile kept stirred at 600 rpm to induce reaction. The reaction solution was cooled to room temperature. The dodecene phase in the upper layer was separated and distilled to expel the unaltered dodecene. The residue of the distillation was treated under a reduced pressure of 2 mmHg in a boiling point range of 129° to 131° C. to obtain 255 g of a secondary dodecanol ethoxylate composition. A reaction vessel of glass, 3000 ml in inner volume, provided with stirring vanes and a reflux condenser The reaction mixture was heated to and reaction The dodecene phase in the upper layer was separated distilled The residue of the distillation was treated under a reduced pressure of 2 mmHg in a boiling point range of 129° to 131° C.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A reaction vessel of glass, 3000 ml in inner volume, provided with stirring vanes and a reflux condenser was charged with 810 g (4.82 mols) of a dodecene-isomer mixture (composed of 25 mol % of 1-dodecene and 75 mol % of inner dodecene) obtained by causing 1-dodecene to react in the liquid phase with 5% by weight of a BEA type zeolite (produced by PQ Corp. and marketed under trademark designation of “VALFOR CP 811 BL-25”) at 150° C. for 10 hours, 900 g (14.52 mols) of monoethylene glycol, and 100 g of the BEA type zeolite (produced by PQ Corp. and marketed under trademark designation of “VALFOR CP 811 BL-25”). The vapor-phase part of the reaction vessel was displaced with nitrogen and then retained in the atmosphere of nitrogen at normal pressure. The reaction mixture was heated to and kept at 150° C. for three hours and meanwhile kept stirred at 600 rpm to induce reaction. The reaction solution was cooled to room temperature. The dodecene phase in the upper layer was separated and distilled to expel the unaltered dodecene. The residue of the distillation was treated under a reduced pressure of 2 mmHg in a boiling point range of 129° to 131° C., to obtain 155 g of a secondary dodecanol ethoxylate composition. A reaction vessel of glass, 3000 ml in inner volume, provided with stirring vanes and a reflux condenser obtained The reaction mixture was heated to and reaction The dodecene phase in the upper layer was separated distilled The residue of the distillation was treated under a reduced pressure of 2 mmHg in a boiling point range of 129° to 131° C.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of DL-phenylalanine 38 (5 g, 30.26 mmol) in toluene (100 mL) was added dodecanol 2 (5.08 g, 27.24 mmol) in one lot, followed by pTSA (6.33 g, 33.29 mmol). The temperature of the reaction mixture was slowly raised to reflux temperature, and the water was separated azeotropically The reaction mixture was monitored by TLC. The reaction mixture was concentrated under vacuum. The obtained residue was taken in ethyl acetate (200 mL) and washed with aqueous 5% Na2CO3 (3×50 mL) followed by brine solution. The organic layer was dried over Na2SO4 and concentrated under vacuum to afford crude 39 (9 g, yield: 89.1%) as a liquid. The temperature of the reaction mixture was slowly raised to reflux temperature the water was separated azeotropically The reaction mixture The reaction mixture was concentrated under vacuum washed with aqueous 5% Na2CO3 (3×50 mL) The organic layer was dried over Na2SO4 concentrated under vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of DL-alanine 1 (5 g, 56.1 mmol) in toluene (100 mL) was added dodecanol 2 (9.42 g, 50.5 mmol) in one lot, followed by pTSA (11.75 g, 61.7 mmol). After addition, the temperature of the reaction mixture was slowly raised to reflux temperature, the water was separated azeotropically, and the reaction mixture was monitored by TLC. The reaction mixture was concentrated under vacuum, the obtained residue was taken in ethyl acetate (200 mL) and washed with aqueous 5% Na2CO3 (3×50 mL) followed by brine solution. The organic layer was dried over Na2SO4 and concentrated under vacuum to afford crude dodecyl 2-aminopropanoate 3 (14.4 g, yield: 100%) as a liquid. After addition the temperature of the reaction mixture was slowly raised to reflux temperature the water was separated azeotropically The reaction mixture was concentrated under vacuum washed with aqueous 5% Na2CO3 (3×50 mL) The organic layer was dried over Na2SO4 concentrated under vacuum