Cyclopropanecarbonyl chloride → 4-(5-carboxymethyl-pyridin-3-yl)-3-[(N-cyclopropanecarbonyl-N-ethyl-amino)-methyl]-benzoic acid

HRID 554588Notes

Reaction equation

HRID 554588 reaction equation
C([O:3][C:4]([CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[CH:21]=[CH:20][C:16]([C:17]([OH:19])=[O:18])=[CH:15][C:14]=2[CH2:22][NH:23][CH2:24][CH3:25])[CH:10]=[N:11][CH:12]=1)=[O:5])C.C(N(C(C)C)CC)(C)C.[CH:35]1([C:38](Cl)=[O:39])[CH2:37][CH2:36]1>C(Cl)Cl>[C:4]([CH2:6][C:7]1[CH:8]=[C:9]([C:13]2[CH:21]=[CH:20][C:16]([C:17]([OH:19])=[O:18])=[CH:15][C:14]=2[CH2:22][N:23]([C:38]([CH:35]2[CH2:37][CH2:36]2)=[O:39])[CH2:24][CH3:25])[CH:10]=[N:11][CH:12]=1)([OH:3])=[O:5]

Participants

5

Reactant 3

HCID 77637Cyclopropanecarbonyl chlorideHCID 81531DiisopropylethylamineHCID 585650534-(5-Ethoxycarbonylmethyl-pyridin-3-yl)-3-ethylaminomethyl-benzoic acid

Product 1

HCID 451383304-(5-carboxymethyl-pyridin-3-yl)-3-[(N-cyclopropanecarbonyl-N-ethyl-amino)-methyl]-benzoic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-(5-Ethoxycarbonylmethyl-pyridin-3-yl)-3-ethylaminomethyl-benzoic acid (0.347 g, 1.0 mmol) and diisopropylethylamine (0.44 mL, 2.5 mmol) were combined in CH2Cl2 (75 mL). Cyclopropanecarbonyl chloride (0.12 mL, 1.3 mmol) was added slowly, and the reaction was stirred at room temperature for 10 minutes. The mixture was quenched with H2O (100 mL), and the product was extracted with CH2Cl2. The combined organic layers were washed with brine and concentrated. The crude material was dissolved in MeOH (75 mL), 1N aqueous LiOH (5 mL) was added and stirred at room temperature for 3 hours. Additional 1N aqueous LiOH (1 mL) was added and the reaction was stirred at room temperature for 3 days. The mixture was quenched with 1N aqueous HCl (5 mL) and extracted with EtOAc. The combined organic layers were washed with H2O and brine, and then concentrated to give 4-(5-carboxymethyl-pyridin-3-yl)-3-[(N-cyclopropanecarbonyl-N-ethyl-amino)-methyl]-benzoic acid.

Workup

  1. customThe mixture was quenched with H2O (100 mL)
  2. extractionthe product was extracted with CH2Cl2
  3. washThe combined organic layers were washed with brine
  4. concentrationconcentrated
  5. dissolutionThe crude material was dissolved in MeOH (75 mL)
  6. addition1N aqueous LiOH (5 mL) was added
  7. stirringstirred at room temperature for 3 hours
  8. additionAdditional 1N aqueous LiOH (1 mL) was added
  9. stirringthe reaction was stirred at room temperature for 3 days
  10. customThe mixture was quenched with 1N aqueous HCl (5 mL)
  11. extractionextracted with EtOAc
  12. washThe combined organic layers were washed with H2O and brine
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-cbe317ccd02c4fe9b4a1bb28f97d93e1
Source dataset
uspto-grants-2011_11
Patent number
US08049015B2

Reaction notes

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