Sodium Hydroxide → Salclobuzate Sodium

HRID 1765473Notes

Reaction equation

HRID 1765473 reaction equation
[Cl:1][C:2]1[CH:16]=[CH:15][C:5]([C:6]([NH:8][CH2:9][CH2:10][CH2:11][C:12]([OH:14])=[O:13])=[O:7])=[C:4]([OH:17])[CH:3]=1.[OH-].[Na+:19]>CC(C)=O>[Cl:1][C:2]1[CH:16]=[CH:15][C:5]([C:6]([NH:8][CH2:9][CH2:10][CH2:11][C:12]([O-:14])=[O:13])=[O:7])=[C:4]([OH:17])[CH:3]=1.[Na+:19]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 98815804-(4-Chloro-2-hydroxybenzamido)butanoic acid

Product 1

HCID 23664294Salclobuzate SodiumYield 97.2%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
50 °C

Procedure

A 22L, five neck round bottom flask, was equipped with an overhead stirrer, reflux condenser, thermocouple temperature read out, and heating mantle. The following reaction was run under a dry nitrogen atmosphere. Reagent acetone (13000 mL) and 4-[(4-chloro-2-hydroxy-benzoyl)amino]butanoic acid (500.0 g, 1.94 mol) were charged to the reactor and stirring was started. The reaction slurry was heated to 50° C. until a hazy brown solution was obtained. The warm solution was pumped through a warm pressure filter dressed with Whatman #1 paper into a clean 22 L reactor. The clear yellow filtrate was heated to 50° C. while stirring. Sodium hydroxide solution (50% aqueous; 155 g, 1.94 mol) was charged to the reactor while maintaining vigorous agitation. After the base addition was complete, the reactor was heated to reflux (60° C.) for 2.5 hours and then allowed to cool slowly to ambient temperature. The product was isolated by vacuum filtration through a sintered glass funnel and dried in a vacuum oven at 50° C. for 24 hours to give 527.3 g of sodium 4-[(4-chloro-2-hydroxybenzoyl)amino]butanoate as an off-white solid. Using acetone in the final stage of the synthesis always resulted in the production of the anhydrous crystalline form. The yield was 97.2%.

Workup

  1. temperaturereflux condenser
  2. temperatureheating mantle
  3. customThe following reaction
  4. customwas obtained
  5. filtrationfilter
  6. customdressed with Whatman #1 paper into a clean 22 L reactor
  7. temperatureThe clear yellow filtrate was heated to 50° C.
  8. stirringwhile stirring
  9. temperaturewhile maintaining vigorous agitation
  10. additionAfter the base addition
  11. temperaturethe reactor was heated
  12. temperatureto reflux (60° C.) for 2.5 hours
  13. temperatureto cool slowly to ambient temperature
  14. customThe product was isolated by vacuum filtration through a sintered glass funnel
  15. customdried in a vacuum oven at 50° C. for 24 hours

Sources & evidence

ORD record
ord-db49b489ae71401d80e535144a2161b3
Source dataset
uspto-grants-2007_06
Patent number
US07227033B2

Reaction notes

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