Veratric Acid → HCID 66653252, compound

HRID 1524307Notes

Reaction equation

HRID 1524307 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[O:12][CH3:13])[C:6]([OH:8])=O.C1N=CN(C(N2C=NC=C2)=O)C=1.CN(C)C=O.[NH2:31][C@@H:32]([C:37]1[CH:38]=[C:39]([CH:43]=[CH:44][CH:45]=1)[C:40]([OH:42])=[O:41])[CH2:33][C:34]([OH:36])=[O:35].CCN(CC)CC>CN(C=O)C>[C:34]([CH2:33][C@H:32]([C:37]1[CH:38]=[C:39]([CH:43]=[CH:44][CH:45]=1)[C:40]([OH:42])=[O:41])[NH:31][C:6](=[O:8])[C:5]1[CH:9]=[CH:10][C:11]([O:12][CH3:13])=[C:3]([O:2][CH3:1])[CH:4]=1)([OH:36])=[O:35]

Participants

6

Reactant 4

HCID 7121Veratric AcidHCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 86667846HCID 86667846, compound

Product 1

HCID 66653252HCID 66653252, compoundYield 36.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Stir a solution of 3,4-dimethoxybenzoic acid (2.318 g, 12.59 mmol) and CDI (2.063 g, 12.59 mmol) in DMF (75 mL) at room temperature for 1 h. To this add 3-((R)-1-amino-2-carboxy-ethyl)-benzoic acid N,N-dimethyl-formamide complex HCl salt (1.606 g, 5.04 mmol) followed by Et3N (2.47 mL, 17.63 mmol), and stir the solution at room temperature for 24 h. Remove the DMF in vacuo at 40° C. and dry the residue to a gum. Redissolve in EtOAc (200 mL). Wash with 0.5 M HCl (200 mL) then water (200 mL) and brine (100 mL). Extract the aqueous layers with more EtOAc (200 mL), and dry the organics (Na2SO4) then concentrate to a gummy residue. Purify this by silica gel chromatography eluting with 50% hexane/EtOAc to 100% EtOAc. Pool fractions containing desired product (Rf=0.10 100% EtOAc) and triturate the residue in EtOAc/hexane to afford 693 mg 3-[(R)-2-carboxy-1-(3,4-dimethoxy-benzoylamino)-ethyl]-benzoic acid as a solid.

Workup

  1. customRemove the DMF in vacuo at 40° C.
  2. customdry the residue to a gum
  3. dissolutionRedissolve in EtOAc (200 mL)
  4. washWash with 0.5 M HCl (200 mL)
  5. extractionExtract the aqueous layers with more EtOAc (200 mL)
  6. dry with materialdry the organics (Na2SO4)
  7. concentrationthen concentrate to a gummy residue
  8. customPurify this by silica gel chromatography
  9. washeluting with 50% hexane/EtOAc to 100% EtOAc
  10. additionPool fractions containing desired product (Rf=0.10 100% EtOAc)
  11. customtriturate the residue in EtOAc/hexane

Sources & evidence

ORD record
ord-53a00368b5a64578bf185a02872aaa92
Source dataset
uspto-grants-2015_07
Patent number
US09079880B2

Reaction notes

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