dodecyl 2-(dimethylamino)propanoate

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

Procedure: DDAIP was prepared by transesterification of ethyl 2-(N,N-dimethylamino)-propionate obtained from Varsal Instruments Inc. (Warminster, Pa.). Specifically, a mixture ethyl 2-(N,N-dimethylamino)-propionate, 1-dodecanol, and sodium methoxide predissolved in toluene was refluxed for about 2 hours. As ethanol formed, it was removed by azeotropic distillation. After about 2 hours of refluxing, the remaining reaction product was filtered to remove solids. was refluxed for about 2 hours it was removed by azeotropic distillation After about 2 hours of refluxing the remaining reaction product was filtered to remove solids

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

Procedure: DDAIP was prepared by transesterification of ethyl 2-(N,N-dimethylamino)-propionate obtained from Varsal Instruments Inc. (Warminster, Pa.). Specifically, a mixture ethyl 2-(N,N-dimethylamino)-propionate, 1-dodecanol, and sodium methoxide predissolved in toluene was refluxed for about 2 hours. As ethanol formed, it was removed by azeotropic distillation. After about 2 hours of refluxing, the remaining reaction product was filtered to remove solids. was refluxed for about 2 hours it was removed by azeotropic distillation After about 2 hours of refluxing the remaining reaction product was filtered to remove solids

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

Procedure: The ethyl 2-(N,N-dimethylamino)-propionate is preferably refluxed for about 2 hours in the presence of 10 percent stoichiometric excess 1-dodecanol and a catalytic amount of sodium methoxide (predissolved in toluene). During this process, the ethanol formed is removed from the reaction medium by azeotropic distillation. Following the reaction phase, the solids of the remaining mixture are filtered off, resulting in a DDAIP filtrate. is removed from the reaction medium by azeotropic distillation the solids of the remaining mixture are filtered off

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

Procedure: The ethyl 2-(N,N-dimethylamino)-propionate is preferably refluxed for about 2 hours in the presence of 10 percent stoichiometric excess 1-dodecanol and a catalytic amount of sodium methoxide (predissolved in toluene). During this process, the ethanol formed is removed from the reaction medium by azeotropic distillation. Following the reaction phase, the solids of the remaining mixture are filtered off, resulting in a DDAIP filtrate. is removed from the reaction medium by azeotropic distillation the solids of the remaining mixture are filtered off

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

Procedure: DDAIP was prepared by transesterification of ethyl 2-(N,N-dimethylamino)-propionate obtained from Varsal Instruments Inc. (Warminster, Pa). Specifically, a mixture ethyl 2-(N,N-dimethylamino)-propionate, 1-dodecanol, and sodium methoxide predissolved in toluene was refluxed for about 2 hours. As ethanol formed, it was removed by azeotropic distillation. After about 2 hours of refluxing, the remaining reaction product was filtered to remove solids. was refluxed for about 2 hours it was removed by azeotropic distillation After about 2 hours of refluxing the remaining reaction product was filtered to remove solids

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

Procedure: A representative reaction scheme follows: ##STR6## The ethyl 2-(N,N-dimethylamino)-propionate is preferably refluxed for about 2 hours in the presence of 10 percent stoichiometric excess 1-dodecanol and a catalytic amount of sodium methoxide (predissolved in toluene). During this process, the ethanol formed is removed from the reaction medium by azeotropic distillation. Following the reaction phase, the solids of the remaining mixture are filtered off, resulting in a DDAIP filtrate. A representative reaction scheme is removed from the reaction medium by azeotropic distillation the solids of the remaining mixture are filtered off

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

Procedure: To a stirred solution of DDAIP base 4 (85 g, 298 mmol) in ethyl acetate (500 mL) cooled to 0° C. was added 2-hydroxyethanesulfonic acid 24 (80% pure only) (45 g, 357 mmol) in one lot. After addition, the temperature of the reaction mixture was slowly raised to room temperature and stirred at RT for 12 h; the reaction mixture was monitored by TLC. The reaction mixture was concentrated under vacuum. The obtained residue was taken in n-hexane (20 mL) and stirred at RT for ½ h (No solid). The obtained sticky solid was kept in deep freezer for 48 h to afford dodecyl 2-(dimethylamino)propanoate 2-hydroxyethanesulfonate salt (25, Nex-46) (125 g, yield: 96.15%) as a waxy hygroscopic solid, Mp: 58-63° C. 1H-NMR (400 MHz, CDCl3): δ 0.8 (t, 31H), 1.2-1.3 (m, 181H), 1.6 (d, 3H), 2.9 (s, 6H), 3.05 (t, 2H), 3.9 (t, 2H), 4.1 (q, 2H), 4.2 (t, 2H); LCMS: 286 (M++1); HPLC: 100%. After addition The reaction mixture was concentrated under vacuum stirred at RT for ½ h (No solid) The obtained sticky solid was kept in deep freezer for 48 h

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

Procedure: A stirred solution of DDAIP base 4 (80 g, 280 mmol) in methanol (500 mL) was cooled to 0° C., then 1,5-napthalene disulfonic acid 22 (50.5 g, 140 mmol) was added in one lot. After addition the temperature of the reaction mixture was slowly raised to RT and stirred at RT for 72 h; the reaction mixture was monitored by TLC. The reaction mixture was concentrated under vacuum and flushed with ethyl acetate (2×30 mL). The obtained residue was taken in n-hexane (200 mL) and stirred at RT for ½ h (sticky solid). The reaction mixture was concentrated under vacuum and flushed with hexane (3×100 mL) to afford dodecyl 2-(dimethylamino)propanoate 1,5-napthalene disulfonate salt (23, Nex-32) (120 g, 92.3%) as a white solid. Mp: 135-140° C. 1H-NMR (400 MHz, CDCl3): δ 0.9 (t, 3H), 1.2-1.3 (m, 18H), 1.6 (d, 3H), 1.65 (q, 2H), 2.9 (s, 6H), 4.15 (t, 2H), 4.2 (q, 1H), 7.55 (t, 2H), 8.22 (d, 2H), 9.1 (d, 2H); LCMS: 286 (M++1); HPLC: 80.48%. After addition the temperature of the reaction mixture The reaction mixture was concentrated under vacuum flushed with ethyl acetate (2×30 mL) stirred at RT for ½ h (sticky solid) The reaction mixture was concentrated under vacuum flushed with hexane (3×100 mL)

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

Procedure: A stirred solution of DDAIP base 4 (85 g, 298 mmol) in ethyl acetate (600 mL) was cooled to 0° C., then ethane sulfonic acid 20 (32.79 g, 298 mmol) was added in one lot. After addition, the temperature of the reaction mixture was slowly raised to RT, stirred at RT for 12 h and the reaction mixture was monitored by TLC. The reaction mixture was concentrated under vacuum and flushed with hexane. The obtained residue was taken in n-hexane (200 mL) and stirred at RT for 2 h (No solid). The obtained sticky solid kept in deep freezer for 12 h to afford dodecyl 2-(dimethylamino)propanoate ethane sulfonate salt (21, Nex-30) (116 g, yield: 98.4%) as a hygroscopic solid, Mp: 45-50° C. 1H-NMR (400 MHz, CDCl3): δ 0.9 (t, 31H), 1.3 (m, 18H), 1.35 (t, 3H), 1.7 (d, 31H), 1.8 (q, 21H), 2.9 (q, 2H), 3 (m, 6H), 4.2 (m, 2H), 4.2 (m, 1H); LCMS: 286 (M++1); HPLC: 99.47%. After addition The reaction mixture was concentrated under vacuum flushed with hexane stirred at RT for 2 h (No solid) The obtained sticky solid kept in deep freezer for 12 h

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

Procedure: A stirred solution of DDAIP base 4 (85 g, 298 mmol) in ethyl acetate (500 mL) was cooled to 0° C., then methane sulfonic acid 18 (28.6 g, 298 mmol) was added in one lot. After addition, the temperature of the reaction mixture was slowly raised to RT and stirred at RT for 48 h; the reaction mixture was monitored by TLC. The reaction mixture was concentrated under vacuum. The obtained residue was taken in n-hexane (30 mL) and stirred at RT for ½ h (No solid). The reaction mixture was concentrated under vacuum and flushed with hexane (3×30 mL) to afford dodecyl 2-(dimethylamino)propanoate methane sulfonate salt (19, Nex-22) (110 g, yield: 97.34%) as a solid, mp: 66-72° C. 1H-NMR (400 MHz, CDCl3): δ 0.9 (t, 3H), 1.35 (m, 18H), 1.65 (q, 2H), 1.7 (d, 3H), 2.8 (s, 3H), 3 (s, 6H), 4.15 (q, 1H), 4.2 (t, 2H); LCMS: 286 (M+); HPLC: 100%. After addition The reaction mixture was concentrated under vacuum stirred at RT for ½ h (No solid) The reaction mixture was concentrated under vacuum flushed with hexane (3×30 mL)

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

Procedure: A stirred solution of DDAIP base 4 (80 g, 280 mmol) in methanol (600 mL) was cooled to 0° C., then maleic acid 16 (32.48 g, 280 mmol) was added in one lot. After addition, the temperature of the reaction mixture was slowly raised to RT and stirred at RT for 12 h; the reaction mixture was monitored by TLC. The reaction mixture was concentrated under vacuum and flushed with ethyl acetate (2×100 mL). The obtained residue was taken in n-hexane (200 mL) and stirred at RT for ½ h (No solid). The reaction mixture was concentrated under vacuum. The obtained sticky solid was kept in deep freezer for 2 h to afford dodecyl 2-(dimethylamino)propanoate maleate salt (17, Nex-20) (111 g, yield: 98.6%) as a solid, mp: 65-70° C. 1H-NMR (400 MHz, CDCl3): δ 0.9 (t, 3H), 1.25 (m, 18H), 1.6 (d, 3H), 1.65 (q, 2H), 2.9 (s, 6H), 4.1 (q, 1H), 4.2 (t, 2H), 6.3 (d, 2H); LCMS: 286 (M++1); HPLC: 80.48%. After addition The reaction mixture was concentrated under vacuum flushed with ethyl acetate (2×100 mL) stirred at RT for ½ h (No solid) The reaction mixture was concentrated under vacuum The obtained sticky solid was kept in deep freezer for 2 h

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

Procedure: A stirred solution of DDAIP base 4 (75 g, 263 mmol) in ethyl acetate (500 mL) was cooled to 0° C., then benzene sulfonic acid 14 (41.55 g, 263 mmol) was added in one lot. After addition, the temperature of the reaction mixture was slowly raised to RT and stirred at RT for 24 h; the reaction mixture was monitored by TLC. The reaction mixture was concentrated under vacuum. The residue washed with hexane (2×30 mL); after workup a sticky solid was observed. The obtained sticky solid was kept in deep freezer for 12 h to afford dodecyl 2-(dimethylamino)propanoate benzene sulfonate salt (15, Nex-16) (116 g, yield: 99.5%) as a solid, mp: 55-62° C. 1H-NMR (400 MHz, CDCl3): δ 0.9 (t, 3H), 1.3 (m, 18H), 1.65 (d, 3H), 1.65 (q, 2H), 3 (s, 6H), 4.2 (q, 1H), 4.2 (t, 2H), 7.4 (m, 3H), 7.9 (d, 2H); LCMS: 286 (M++1); HPLC: 80.48%. After addition The reaction mixture was concentrated under vacuum The residue washed with hexane (2×30 mL) The obtained sticky solid was kept in deep freezer for 12 h