(2R,3R,4R,5S)-6-(octylamino)hexane-1,2,3,4,5-pentol

Conditions: temp:33.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Racemic ibuprofen (27.03, 131.03 mmol), N-octyl-D-glucamine (16.35 g, 55.73 mmol), and isopropanol (150 mL) were heated to 80° C., forming a clear solution, and the solution then cooled to 33° C. over 4 hours. The resulting precipitate was recovered by filtration, washed with isopropanol, and dried to give (S)-ibuprofen N-octyl-D-glucamine salt (23.95 g, 47.93 mmol, 73.2% yield, 99.0% ee). forming a clear solution The resulting precipitate was recovered by filtration washed with isopropanol dried

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Racemic ibuprofen (18.03 g, 87.4 mmol), N-octyl-D-glucamine (12.12 g, 41.3 mmol), triethylamine (8.6 g, 88 mmol), water (0.5 mL), and toluene (150 mL) were heated to 80° C., forming a clear solution. The solution was cooled slowly to 25° C. The resulting crystalline precipitate was recovered by filtration, washed with toluene, and dried to give (S)-ibuprofen N-octyl-D-glucamine salt (18.0 g, 82.4% yield, 86.4% ee). forming a clear solution The resulting crystalline precipitate was recovered by filtration washed with toluene dried

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Racemic ibuprofen (18.03 g, 87.4 mmol), N-octyl-D-glucamine (12.12 g, 41.3 mmol), triethylamine (4.4 g, 43.5 mmol), water (0.5 mL), and toluene (150 mL) were heated to 80° C., forming a clear solution. The solution was cooled to 25° C. over 2 1/2 hours, then cooled in an ice bath to 15° C. The resulting crystalline precipitate was recovered by filtration, washed with toluene, and dried to give (S)-ibuprofen N-octyl-D-glucamine salt (17.2 g, 78.8% yield, 94.8% ee). forming a clear solution cooled in an ice bath to 15° C The resulting crystalline precipitate was recovered by filtration washed with toluene dried

Conditions: temp:15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Second resolution. The racemic ibuprofen from the previous step and fresh racemic ibuprofen (5.8 g) were dissolved in toluene (150 mL), and water (0.5 mL) and N-octyl-D-glucamine (12.12 g, 41 mmol) were added to the solution. This mixture was heated to 75° C., forming a clear solution, and the solution cooled to 20° C. over 4 hours. The resulting precipitate was recovered by filtration, washed with toluene (50 mL), and dried to give (S)-ibuprofen N-octyl-D-glucamine salt (13.85 g). The (S)-ibuprofen N-octyl-D-glucamine salt was stirred with water (50 mL) and KOH (2.2 g) at 45° C. for one hour, and the mixture then cooled to 15° C. The resulting precipitate was recovered by filtration, washed with water (50 mL), and dried to give N-octyl-D-glucamine (7.3 g) for recycle. The aqueous filtrate from recovery of the N-octyl-D-glucamine was acidified with 3N HCl to pH<1. The resulting precipitate was recovered by filtration to give (S)-ibuprofen (5.35 g, 58% yield, MR=50.5°-51° C., 99% ee). The resulting precipitate was recovered by filtration washed with water (50 mL) dried

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Second resolution. The racemic ibuprofen from the previous step and fresh racemic ibuprofen (5.8 g) were dissolved in toluene (150 mL), and water (0.5 mL) and N-octyl-D-glucamine (12.12 g, 41 mmol) were added to the solution. This mixture was heated to 75° C., forming a clear solution, and the solution cooled to 20° C. over 4 hours. The resulting precipitate was recovered by filtration, washed with toluene (50 mL), and dried to give (S)-ibuprofen N-octyl-D-glucamine salt (13.85 g). The (S)-ibuprofen N-octyl-D-glucamine salt was stirred with water (50 mL) and KOH (2.2 g) at 45° C. for one hour, and the mixture then cooled to 15° C. The resulting precipitate was recovered by filtration, washed with water (50 mL), and dried to give N-octyl-D-glucamine (7.3 g) for recycle. The aqueous filtrate from recovery of the N-octyl-D-glucamine was acidified with 3N HCl to pH<1. The resulting precipitate was recovered by filtration to give (S)-ibuprofen (5.35 g, 58% yield, MR=50.5°-51° C., 99% ee). forming a clear solution the solution cooled to 20° C. over 4 hours The resulting precipitate was recovered by filtration washed with toluene (50 mL) dried

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Initial resolution. Racemic ibuprofen (18 g, 87 mmol) was dissolved in toluene (150 mL), and water (0.5 mL) and N-octyl-D-glucamine (12.12 g, 41 mmol) were added to the solution. The mixture was heated slowly to 75° C., forming a clear solution, and the solution then cooled to 20° C. over 3 hours. The resulting precipitate was recovered by filtration, washed with toluene (50 mL), and dried to give (S)-ibuprofen N-octyl-D-glucamine salt (14.75 g, 30 mmol, MR=136.5°~137° C., [α]D =-11.2° (c=0.1, MeOH), 99% ee). The toluene liquors were saved for racemization and recycle of the contained (R)-ibuprofen. forming a clear solution the solution then cooled to 20° C. over 3 hours The resulting precipitate was recovered by filtration washed with toluene (50 mL) dried

Conditions: temp:78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Racemic ibuprofen (80 g, 390 mmol), toluene (200 mL), and water (0.5 mL) were stirred at 40° C., and N-octyl-D-glucamine (53.8 g, 183 mmol, N-octyl-D-glucamine/(S)-ibuprofen molar ratio=0.938) was added to the solution. The resulting thick slurry was heated to 78° C., forming a clear solution, and the solution then cooled to 15° C. over 3-4 hours. The resulting precipitate was recovered by filtration, washed with toluene (100 mL), and dried to give (S)-ibuprofen N-octyl-D-glucamine salt (72.2 g, 145 mmol, 74.6% yield, MR=136°-137° C.). The toluene liquors were saved for racemization and recycle of the contained (R)-ibuprofen. forming a clear solution the solution then cooled to 15° C. over 3-4 hours The resulting precipitate was recovered by filtration washed with toluene (100 mL) dried

Conditions: temp:33.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Racemic ibuprofen (27.03, 131.03 mmol), N-octyl-D-glucamine (16.35 g, 55.73 mmol), and isopropanol (150 mL) were heated to 80° C., forming a clear solution, and the solution then cooled to 33° C. over 4 hours. The resulting precipitate was recovered by filtration, washed with isopropanol, and dried to give (S)-ibuprofen N-octyl-D-glucamine salt (23.95 g, 47.93 mmol, 73.2% yield, 99.0% ee). forming a clear solution The resulting precipitate was recovered by filtration washed with isopropanol dried

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Racemic ibuprofen (18.03 g, 87.4 mmol), N-octyl-D-glucamine (12.12 g, 41.3 mmol), triethylamine (8.6 g, 88 mmol), water (0.5 mL), and toluene (150 mL) were heated to 80° C., forming a clear solution. The solution was cooled slowly to 25° C. The resulting crystalline precipitate was recovered by filtration, washed with toluene, and dried to give (S)-ibuprofen N-octyl-D-glucamine salt (18.0 g, 82.4% yield, 86.4% ee). forming a clear solution The resulting crystalline precipitate was recovered by filtration washed with toluene dried

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Racemic ibuprofen (18.03 g, 87.4 mmol), N-octyl-D-glucamine (12.12 g, 41.3 mmol), triethylamine (4.4 g, 43.5 mmol), water (0.5 mL), and toluene (150 mL) were heated to 80° C., forming a clear solution. The solution was cooled to 25° C. over 2 1/2 hours, then cooled in an ice bath to 15° C. The resulting crystalline precipitate was recovered by filtration, washed with toluene, and dried to give (S)-ibuprofen N-octyl-D-glucamine salt (17.2 g, 78.8% yield, 94.8% ee). forming a clear solution cooled in an ice bath to 15° C The resulting crystalline precipitate was recovered by filtration washed with toluene dried

Conditions: temp:15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Second resolution. The racemic ibuprofen from the previous step and fresh racemic ibuprofen (5.8 g) were dissolved in toluene (150 mL), and water (0.5 mL) and N-octyl-D-glucamine (12.12 g, 41 mmol) were added to the solution. This mixture was heated to 75° C., forming a clear solution, and the solution cooled to 20° C. over 4 hours. The resulting precipitate was recovered by filtration, washed with toluene (50 mL), and dried to give (S)-ibuprofen N-octyl-D-glucamine salt (13.85 g). The (S)-ibuprofen N-octyl-D-glucamine salt was stirred with water (50 mL) and KOH (2.2 g) at 45° C. for one hour, and the mixture then cooled to 15° C. The resulting precipitate was recovered by filtration, washed with water (50 mL), and dried to give N-octyl-D-glucamine (7.3 g) for recycle. The aqueous filtrate from recovery of the N-octyl-D-glucamine was acidified with 3N HCl to pH<1. The resulting precipitate was recovered by filtration to give (S)-ibuprofen (5.35 g, 58% yield, MR=50.5°-51° C., 99% ee). The resulting precipitate was recovered by filtration washed with water (50 mL) dried

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Second resolution. The racemic ibuprofen from the previous step and fresh racemic ibuprofen (5.8 g) were dissolved in toluene (150 mL), and water (0.5 mL) and N-octyl-D-glucamine (12.12 g, 41 mmol) were added to the solution. This mixture was heated to 75° C., forming a clear solution, and the solution cooled to 20° C. over 4 hours. The resulting precipitate was recovered by filtration, washed with toluene (50 mL), and dried to give (S)-ibuprofen N-octyl-D-glucamine salt (13.85 g). The (S)-ibuprofen N-octyl-D-glucamine salt was stirred with water (50 mL) and KOH (2.2 g) at 45° C. for one hour, and the mixture then cooled to 15° C. The resulting precipitate was recovered by filtration, washed with water (50 mL), and dried to give N-octyl-D-glucamine (7.3 g) for recycle. The aqueous filtrate from recovery of the N-octyl-D-glucamine was acidified with 3N HCl to pH<1. The resulting precipitate was recovered by filtration to give (S)-ibuprofen (5.35 g, 58% yield, MR=50.5°-51° C., 99% ee). forming a clear solution the solution cooled to 20° C. over 4 hours The resulting precipitate was recovered by filtration washed with toluene (50 mL) dried