Acetic Acid → HCID 45106180, compound

HRID 1971325Notes

Reaction equation

HRID 1971325 reaction equation
[NH2:1][CH:2]([C:7]1[CH:12]=[C:11]([O:13][CH3:14])[C:10]([O:15][CH3:16])=[C:9]([O:17][CH3:18])[CH:8]=1)[CH2:3][C:4]([OH:6])=[O:5].[C:19]1([CH:27]=O)[C:20]([CH:25]=[O:26])=[CH:21][CH:22]=[CH:23][CH:24]=1.C(O)(=O)C>ClCCl>[O:26]=[C:25]1[C:20]2[C:19](=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:27][N:1]1[CH:2]([C:7]1[CH:8]=[C:9]([O:17][CH3:18])[C:10]([O:15][CH3:16])=[C:11]([O:13][CH3:14])[CH:12]=1)[CH2:3][C:4]([OH:6])=[O:5]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 4807PhthalaldehydeHCID 33126913-amino-3-(3,4,5-trimethoxyphenyl)propanoic acid

Product 1

HCID 45106180HCID 45106180, compoundYield 20%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3-Amino-3-(3,4,5-trimethoxy-phenyl)-propionic acid (3.66 mmol, 1 eq), benzene-1,2-dicarbaldehyde (1 eq) and acetic acid (16 eq) are suspended in dichloromethane and refluxed for 2 h. The filtrate is concentrated in vacuo, dissolved in DCM and extracted with water. The organic phase is reduced under vacuum. The resulting oil is suspended in 1 M NaOH and stirred for 30 min at room temperature. The solution is washed with EtOAc and the aqueous phase is acidified with 1 M HCl (pH 2) and extracted with EtOAc. The organic phase is reduced under vacuum, dissolved in DCM and 3-(4-(hydrazinosulfonyl)phenyl)propionyl AM resin is added. The suspension is shaken at rt for 16 h. The filtrate is concentrated in vacuo, dissolved in DMSO and purified by prep. LC/MS (reversed phase). 3-(1-Oxo-1,3-dihydro-isoindole-2-yl)-3-(3,4,5-trimethoxy-phenyl)-propionic acid is obtained as a clear colourless film (20% yield); ES-MS (MH+)=372.0; mp. 162-164° C.; 1H-NMR (DMSO-d6, 300 MHz): δ [ppm] 12.37 (br s, 1H), 7.69 (d, 1H, 7.6 Hz), 7.62-7.45 (m, 3H), 6.70 (s, 2H), 5.68 (t, 1H, 7.9 Hz); 4.53 (d, 1H, 17.9 Hz), 4.20 (d, 1H, 17.9 Hz), 3.76 (s, 6H), 3.63 (s, 3H), 3.14 (d, 2H, 7.9 Hz).

Workup

  1. temperaturerefluxed for 2 h
  2. concentrationThe filtrate is concentrated in vacuo
  3. dissolutiondissolved in DCM
  4. extractionextracted with water
  5. washThe solution is washed with EtOAc
  6. extractionextracted with EtOAc
  7. dissolutiondissolved in DCM
  8. additionis added
  9. stirringThe suspension is shaken at rt for 16 h
  10. concentrationThe filtrate is concentrated in vacuo
  11. dissolutiondissolved in DMSO
  12. custompurified by prep

Sources & evidence

ORD record
ord-5788768b45de4dffbde74320abb71587
Source dataset
uspto-grants-2013_04
Patent number
US08431602B2

Reaction notes

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