Dichloromethane → 4-Acryloylamino-5-chloro-2-hydroxybenzoic acid methyl ester

HRID 273174

Reaction equation

HRID 273174 reaction equation
[CH3:1][O:2][C:3](=[O:13])[C:4]1[CH:9]=[C:8]([Cl:10])[C:7]([NH2:11])=[CH:6][C:5]=1[OH:12].C(Cl)Cl.[C:17](Cl)(=[O:20])[CH:18]=[CH2:19]>C(N(CC)CC)C>[CH3:1][O:2][C:3](=[O:13])[C:4]1[CH:9]=[C:8]([Cl:10])[C:7]([NH:11][C:17](=[O:20])[CH:18]=[CH2:19])=[CH:6][C:5]=1[OH:12]

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 13140Acryloyl chlorideHCID 14883223Methyl 4-amino-5-chloro-2-hydroxybenzoate

Product 1

HCID 686921384-Acryloylamino-5-chloro-2-hydroxybenzoic acid methyl ester

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Conditions

Temperature
0 °C

Procedure

To 4-amino-5-chloro-2-hydroxybenzoic acid methyl ester, was added DCM and triethylamine. This mixture was cooled to 0° C. and acryloyl chloride was added dropwise with stirring. After approximately 2 hours, the reaction was quenched by adding MeOH at 0° C. and the resulting mixture was stirred at room temperature for about 15 min and then concentrated in vacuo. DCM and water were added to the residue and this mixture was mixed thoroughly. The layers were separated and the aqueous layer was extracted with DCM. The organic layers were combined, dried (Na2SO4), filtered and the solvent was removed in vacuo to give 4-acryloylamino-5-chloro-2-hydroxybenzoic acid methyl ester. This ester was then combined with Preparation 1, followed by the addition of a THF-MeOH solvent. The mixture was heated and stirred for about 16 hours to provide biphenyl-2-ylcarbamic acid 1-[2-(4-formyl-3-hydroxyphenylcarbamoyl)ethyl]piperidin-4-yl ester was made. Using this ester, and following the procedure described in Example 2 and substituting the appropriate amine, the title compound was prepared. MS m/z [M+H+] calcd for C35H38N4O5, 595.7; found, 595.2.

Workup

  1. customthe reaction was quenched
  2. additionby adding MeOH at 0° C.
  3. stirringthe resulting mixture was stirred at room temperature for about 15 min
  4. concentrationconcentrated in vacuo
  5. additionDCM and water were added to the residue
  6. additionthis mixture was mixed thoroughly
  7. customThe layers were separated
  8. extractionthe aqueous layer was extracted with DCM
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-a1a1aaca76744c19ad1fa0d64b1e267e
Source dataset
uspto-grants-2008_11
Patent number
US07456199B2

Linked notes

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