Hydrochloric Acid → Hydroxy Tipelukast

HRID 486122Notes

Reaction equation

HRID 486122 reaction equation
Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[C:7]([CH2:22][CH2:23][CH3:24])=[C:8]([C:16]([CH:19]([OH:21])[CH3:20])=[CH:17][CH:18]=1)[O:9][CH2:10][CH2:11][CH2:12][C:13]([OH:15])=[O:14].[OH:25][C:26]1[C:31]([CH2:32][CH2:33][CH3:34])=[C:30]([SH:35])[CH:29]=[CH:28][C:27]=1[C:36](=[O:38])[CH3:37].C(=O)([O-])[O-].[K+].[K+].Cl>CN(C)C=O>[C:36]([C:27]1[CH:28]=[CH:29][C:30]([S:35][CH2:2][CH2:3][CH2:4][O:5][C:6]2[C:7]([CH2:22][CH2:23][CH3:24])=[C:8]([C:16]([CH:19]([OH:21])[CH3:20])=[CH:17][CH:18]=2)[O:9][CH2:10][CH2:11][CH2:12][C:13]([OH:15])=[O:14])=[C:31]([CH2:32][CH2:33][CH3:34])[C:26]=1[OH:25])(=[O:38])[CH3:37]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 132955181-(2-Hydroxy-3-propyl-4-sulfanylphenyl)ethan-1-oneHCID 54321325HCID 54321325, compound

Product 1

HCID 9828483Hydroxy TipelukastYield 35.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixed solution of 55.9 mg of (-)-4-[3-(3-chloropropoxy)-6-(1-hydroxyethyl)-2-propylphenoxy] butanoic acid, 39.3 mg of (2-hydroxy-4-mercapto-3-propylphenyl) ethanone, 51.7 mg of potassium carbonate and 1 ml of dimethylformamide was stirred at room temperature for 6 hours. The reaction mixture was poured into ice water, acidified with 1N-hydrochloric acid, and extracted with ethyl acetate. After washed with water and saturated aqueous solution of sodium chloride, the organic layer was dried over anhydrous sodium sulfate and subjected to distillation off of the solvent under reduced pressure to afford residue, which was then purified through silica gel column chromatography (methylene chloride: methanol=20:1) and further purified through preparative thin layer chromatography (methylene chloride: methanol=15:1) to afford 29.8 mg of yellow oily matter as the title compound (35.9%). [α]D20 -13.8° (c=2.98, ethanol)

Workup

  1. extractionextracted with ethyl acetate
  2. washAfter washed with water and saturated aqueous solution of sodium chloride
  3. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  4. distillationsubjected to distillation off of the solvent under reduced pressure
  5. customto afford residue, which
  6. customwas then purified through silica gel column chromatography (methylene chloride: methanol=20:1)
  7. customfurther purified through preparative thin layer chromatography (methylene chloride: methanol=15:1)

Sources & evidence

ORD record
ord-53511a9e05cd4d08b7bab8f742ccf7e2
Source dataset
uspto-grants-1994_03
Patent number
US05290812

Reaction notes

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