Water → (S)-ibuprofen N-octyl-D-glucamine salt

HRID 54033

Reaction equation

HRID 54033 reaction equation
[OH:1][C:2]([CH:4]([C:6]1[CH:15]=[CH:14][C:9]([CH2:10][CH:11]([CH3:13])[CH3:12])=[CH:8][CH:7]=1)[CH3:5])=[O:3].O.[CH2:17]([NH:25][CH2:26][C@@H:27]([C@H:29]([C@@H:31]([C@@H:33]([CH2:35][OH:36])[OH:34])[OH:32])[OH:30])[OH:28])[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24]>C1(C)C=CC=CC=1>[CH2:17]([NH:25][CH2:26][C@@H:27]([C@H:29]([C@@H:31]([C@@H:33]([CH2:35][OH:36])[OH:34])[OH:32])[OH:30])[OH:28])[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24].[OH:3][C:2]([C@H:4]([C:6]1[CH:7]=[CH:8][C:9]([CH2:10][CH:11]([CH3:12])[CH3:13])=[CH:14][CH:15]=1)[CH3:5])=[O:1]

Participants

5

Reactant 3

HCID 962WaterHCID 3672Ibuprofen, (+-)-2×HCID 900641-Deoxy-1-(octylamino)-D-glucitol

Product 1

HCID 131719976(S)-ibuprofen N-octyl-D-glucamine salt

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
75 °C

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).

Workup

  1. customforming a clear solution
  2. temperaturethe solution cooled to 20° C. over 4 hours
  3. filtrationThe resulting precipitate was recovered by filtration
  4. washwashed with toluene (50 mL)
  5. customdried

Sources & evidence

ORD record
ord-6470614f2d8c4a32826a822b5b59b05f
Source dataset
uspto-grants-1997_04
Patent number
US05621140

Linked notes

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