Sodium Hydroxide → Salclobuzate Sodium

HRID 2374105Notes

Reaction equation

HRID 2374105 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 22 L, 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. customA 22 L, five neck round bottom flask, was equipped with an overhead stirrer
  2. temperaturereflux condenser
  3. temperatureheating mantle
  4. customThe following reaction
  5. customwas obtained
  6. filtrationfilter
  7. customdressed with Whatman #1 paper into a clean 22 L reactor
  8. temperatureThe clear yellow filtrate was heated to 50° C.
  9. stirringwhile stirring
  10. temperaturewhile maintaining vigorous agitation
  11. additionAfter the base addition
  12. temperaturethe reactor was heated
  13. temperatureto reflux (60° C.) for 2.5 hours
  14. temperatureto cool slowly to ambient temperature
  15. customThe product was isolated by vacuum filtration through a sintered glass funnel
  16. customdried in a vacuum oven at 50° C. for 24 hours

Sources & evidence

ORD record
ord-5fa75f59b3c546dbaac0e65705f9880b
Source dataset
uspto-grants-2008_12
Patent number
US07462368B2

Reaction notes

Loading…