Acetic Acid → Montelukast

HRID 644784

Reaction equation

HRID 644784 reaction equation
[CH3:1][C:2]([OH:41])([C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][C:9]=1[CH2:10][CH2:11][C@@H:12]([S:32][CH2:33][C:34]1([CH2:37][C:38]([OH:40])=[O:39])[CH2:36][CH2:35]1)[C:13]1[CH:14]=[CH:15][CH:16]=[C:17](/[CH:19]=[CH:20]/[C:21]2[CH:22]=[CH:23][C:24]3[CH:25]=[CH:26][C:27]([Cl:31])=[CH:28][C:29]=3[N:30]=2)[CH:18]=1)[CH3:3].C1(N)CCCCC1.C(O)(=O)C>C1(C)C=CC=CC=1>[CH3:3][C:2]([OH:41])([C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][C:9]=1[CH2:10][CH2:11][C@@H:12]([S:32][CH2:33][C:34]1([CH2:37][C:38]([OH:40])=[O:39])[CH2:35][CH2:36]1)[C:13]1[CH:14]=[CH:15][CH:16]=[C:17](/[CH:19]=[CH:20]/[C:21]2[CH:22]=[CH:23][C:24]3[CH:25]=[CH:26][C:27]([Cl:31])=[CH:28][C:29]=3[N:30]=2)[CH:18]=1)[CH3:1]

Participants

4

Reactant 2

HCID 176Acetic AcidHCID 24823153Montelukast cyclohexylamine

Product 1

HCID 5281040Montelukast

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Montelukast cyclohexylamine salt suspended in toluene (5 parts) was treated with aqueous acetic acid (5 parts) until a pH of 5.0˜5.5 was reached. The organic phase was separated and washed with water (5 parts) twice, and the resulting organic layer was concentrated to provide a crude oil of montelukast acid. The montelukast acid (100.0 g, 170.2 mmol) thus obtained was dissolved in 500 mL THF, and then 78 mL of ca. 2N NaOH aqueous solution was added under nitrogen. After stirring for several minutes, the solvent was removed under reduced pressure at 30° C. to afford montelukast sodium as a crude oil. The crude oil was taken up in 2.5 L water and concentrated to remove the remaining THF until the total volume was about 2.7 L (THF remained as analyzed by GC was 1.7%). The aqueous solution of montelukast sodium was filtered, and its purity was determined by HPLC (99.7%). The filtered solution was subjected to spray drying at various conditions, and the results were listed in Table 5.

Workup

  1. customThe organic phase was separated
  2. washwashed with water (5 parts) twice
  3. concentrationthe resulting organic layer was concentrated

Sources & evidence

ORD record
ord-0b24fea6d0864ddba12b529653ee5bf0
Source dataset
uspto-grants-2010_04
Patent number
US07700776B2

Linked notes

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