Dichloromethane → 4-(9-Carboxy-nonanoylamino)-2-hydroxybenzamide

HRID 1746243Notes

Reaction equation

HRID 1746243 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([OH:11])[C:5](=[CH:9][CH:10]=1)[C:6]([NH2:8])=[O:7].C(Cl)Cl.Cl[C:16](=[O:29])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][C:25]([O:27]C)=[O:26]>C(N(CC)CC)C>[C:25]([CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][C:16]([NH:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH2:8])=[O:7])=[C:4]([OH:11])[CH:3]=1)=[O:29])([OH:27])=[O:26]

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 4594244-Amino-2-hydroxybenzamideHCID 544219Methyl 10-chloro-10-oxodecanoate

Product 1

HCID 251229714-(9-Carboxy-nonanoylamino)-2-hydroxybenzamide

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

4-aminosalicylamide (2 g) from Example 5 is charged with 20 mL of methylene chloride. To the solution, 3.3 g of methyl 10-chloro-10-oxodecanoate is added. The reaction is initiated by addition of 2.6 mL of triethylamine. The reaction mixture is allowed to stir at ambient conditions for 2 days. Solvent is removed and the residue is acidified using 1 N HCl. The precipitate is extracted into ethyl acetate. The organic layer is further extracted with 1 N NaOH and saturated NaCl solutions. After drying over anhydrous sodium sulfate, solvent is removed. The residue is reconstituted in tetrahydrofuran (10 mL) and 10 mL of 2 N NaOH is added. The solution is brought to gentle reflux for 2 hours. The disappearance of the methyl ester is followed by HPLC. When all ester is hydrolyzed, the solution is cooled and acidified and the product is extracted into ethyl acetate. The organic layer is washed with saturated NaCl and dried over anhydrous sodium sulfate. Solvent is removed under reduced pressure and the product is obtained as off-white powder.

Workup

  1. customSolvent is removed
  2. extractionThe precipitate is extracted into ethyl acetate
  3. extractionThe organic layer is further extracted with 1 N NaOH and saturated NaCl solutions
  4. dry with materialAfter drying over anhydrous sodium sulfate, solvent
  5. customis removed
  6. addition10 mL of 2 N NaOH is added
  7. temperatureto gentle reflux for 2 hours
  8. temperaturethe solution is cooled
  9. extractionthe product is extracted into ethyl acetate
  10. washThe organic layer is washed with saturated NaCl
  11. dry with materialdried over anhydrous sodium sulfate
  12. customSolvent is removed under reduced pressure
  13. customthe product is obtained as off-white powder

Sources & evidence

ORD record
ord-fbf578cc061a4c09a9e60ef658c9a55f
Source dataset
uspto-grants-2015_10
Patent number
US09149530B2

Reaction notes

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