3-(3'-Hydroxyphenyl)propionic acid → Methyl 4-{[3-(3-hydroxyphenyl)propanoyl]amino}benzoate

HRID 642117Notes

Reaction equation

HRID 642117 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][C:10]([OH:12])=O)[CH:5]=[CH:6][CH:7]=1.CN1CCOCC1.C(OC(Cl)=O)C(C)C.[NH2:28][C:29]1[CH:38]=[CH:37][C:32]([C:33]([O:35][CH3:36])=[O:34])=[CH:31][CH:30]=1>C1COCC1>[OH:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][C:10]([NH:28][C:29]2[CH:30]=[CH:31][C:32]([C:33]([O:35][CH3:36])=[O:34])=[CH:37][CH:38]=2)=[O:12])[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 913-(3'-Hydroxyphenyl)propionic acidHCID 79724-MethylmorpholineHCID 12082Methyl 4-aminobenzoateHCID 62365Isobutyl chloroformate

Product 1

HCID 68409251Methyl 4-{[3-(3-hydroxyphenyl)propanoyl]amino}benzoateYield 32%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 3-(3-hydroxyphenyl)-propionic acid (198 mg, 1.19 mmol) in anhydrous THF (5 mL) were added N-methylmorpholine (1.2 equiv.) and isobutylchloroformate (1.2 equiv.) at 0° C. After 30 min, at 0° C., a solution of methyl 4-aminobenzoate (150 mg, 0.99 mmol) in anhydrous THF (1 mL) was added to the reaction mixture. After 5 min the temperature was allowed to warm up to rt and stir overnight. After extraction with EtOAc (100 mL), washing with HCl (0.1N, 50 mL) and a saturated aqueous solution of NaHCO3 (50 mL), the organic layer was dryed over sodium sulfate and evaporated under vacuo to give a yellow oil. Purification by flash chromatography using EtOAc/cyclohexane as eluant and recrystallization from DCM/MeOH/TEA (10/0.4/0.1) gave the title compound as a white solid (32%) in 98.9% purity by HPLC (MaxPlot detection between 230 and 400 nm).

Workup

  1. waitAfter 5 min the temperature was allowed
  2. extractionAfter extraction with EtOAc (100 mL)
  3. washwashing with HCl (0.1N, 50 mL)
  4. customevaporated under vacuo
  5. customto give a yellow oil
  6. customPurification by flash chromatography
  7. customrecrystallization from DCM/MeOH/TEA (10/0.4/0.1)

Sources & evidence

ORD record
ord-e29aac5a86d041d58b68ec7d2515d364
Source dataset
uspto-grants-2010_04
Patent number
US07696231B2

Reaction notes

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