Toluene → Montelukast Sodium

HRID 1931357Notes

Reaction equation

HRID 1931357 reaction equation
C1(C)C=CC=CC=1.[CH3:8][C:9]([OH:48])([C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][C:16]=1[CH2:17][CH2:18][C@@H:19]([S:39][CH2:40][C:41]1([CH2:44][C:45]([OH:47])=[O:46])[CH2:43][CH2:42]1)[C:20]1[CH:21]=[CH:22][CH:23]=[C:24](/[CH:26]=[CH:27]/[C:28]2[CH:29]=[CH:30][C:31]3[CH:32]=[CH:33][C:34]([Cl:38])=[CH:35][C:36]=3[N:37]=2)[CH:25]=1)[CH3:10].[OH-].[Na+:50].CCCCCCC>CO>[CH3:10][C:9]([OH:48])([C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][C:16]=1[CH2:17][CH2:18][C@@H:19]([S:39][CH2:40][C:41]1([CH2:44][C:45]([O-:47])=[O:46])[CH2:42][CH2:43]1)[C:20]1[CH:21]=[CH:22][CH:23]=[C:24](/[CH:26]=[CH:27]/[C:28]2[CH:29]=[CH:30][C:31]3[CH:32]=[CH:33][C:34]([Cl:38])=[CH:35][C:36]=3[N:37]=2)[CH:25]=1)[CH3:8].[Na+:50]

Participants

6

Reactant 4

HCID 1140TolueneHCID 8900HeptaneHCID 14798Sodium HydroxideHCID 5281040Montelukast

Product 1

HCID 23663996Montelukast SodiumYield 100%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

1.15 L of toluene were added to 115.2 g of Montelukast acid (e.e.: 99.9%). The mixture was cooled between 2 and 10° C. and 313.3 ml of 0.5M NaOH solution in methanol were added over 15 minutes. Then, the mixture was warmed to room temperature and stirred for 30 minutes. After this period of time, 1.5 L of the solvent were distilled off under reduced pressure at 30° C. Then, 2.4 L of toluene were charged to the crude and the distillation was resumed to obtain a final volume of 300 ml. The solution of crude obtained was added over 1 hour to 1 L of heptane under stirring at room temperature. 18 hours after the addition, an off white solid was filtered off under a nitrogen atmosphere and washed with 500 ml of heptane. The wet product was dried under vacuum at 75° C. for 3 days to yield 120 g of Montelukast sodium. Yield: 100%. e.e.: 99.9%.

Workup

  1. temperatureThe mixture was cooled between 2 and 10° C.
  2. distillationAfter this period of time, 1.5 L of the solvent were distilled off under reduced pressure at 30° C
  3. additionThen, 2.4 L of toluene were charged to the crude
  4. distillationthe distillation
  5. customto obtain a final volume of 300 ml
  6. customThe solution of crude obtained
  7. stirringunder stirring at room temperature
  8. addition18 hours after the addition
  9. filtrationan off white solid was filtered off under a nitrogen atmosphere
  10. washwashed with 500 ml of heptane
  11. customThe wet product was dried under vacuum at 75° C. for 3 days

Sources & evidence

ORD record
ord-fb74722c80b44c3082b3b95e446a9999
Source dataset
uspto-grants-2012_05
Patent number
US08188285B2

Reaction notes

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