2-Phenylpropionic acid → HCID 18334080, compound

HRID 2269416Notes

Reaction equation

HRID 2269416 reaction equation
C(Cl)(=O)C(Cl)=O.[C:7]1([CH:13]([CH3:17])[C:14]([OH:16])=O)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.C[O:19][C:20]1[C:21](=[O:41])[C:22](=O)[C:23]=1[NH:24][C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([NH:31][C:32]2[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][CH:33]=2)[CH:26]=1.C[N:43](C)C(=O)C>CN(C)C=O.C(Cl)Cl>[NH2:43][C:22]1[C:21](=[O:41])[C:20](=[O:19])[C:23]=1[NH:24][C:25]1[CH:26]=[C:27]([N:31]([C:32]2[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][CH:33]=2)[C:14](=[O:16])[CH:13]([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH3:17])[CH:28]=[CH:29][CH:30]=1

Participants

7

Reactant 4

HCID 102962-Phenylpropionic acidHCID 31374Dimethylacetamide2×HCID 65578Oxalyl chlorideHCID 18347028HCID 18347028, compound

Product 1

HCID 18334080HCID 18334080, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

Oxalyl chloride (0.8 ml) and N,N-dimethylformamide (1 drop) were added to a solution of 2-phenylpropionic acid (900 mg) in methylene chloride (10 ml). This mixture was stirred at ambient temperature for 2 hours. The reaction mixture was then concentrated by evaporation under reduced pressure to afford a yellow oil. A solution of 3-methoxy-4-[3-(4-methoxyphenylamino)phenyl]amino-3-cyclobutene-1,2-dione (576 mg) [prepared as described in step (a) above] in N,N-dimethylacetamide (4 ml) was added to a solution of the oil in N,N-dimethylacetamide (4 ml) in an ice bath. The mixture was stirred at ambient temperature for 3 hours. At the end of this time, the reaction mixture was partitioned between a saturated aqueous solution of sodium hydrogencarbonate and ethyl acetate. The ethyl acetate layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and concentrated by evaporation under reduced pressure. The residue was purified by chromatography through a silica gel column using a 2:1 by volume mixture of methylene chloride and ethyl acetate as the eluant, to afford the title compound (603 mg) as a purple foamy solid.

Workup

  1. concentrationThe reaction mixture was then concentrated by evaporation under reduced pressure
  2. customto afford a yellow oil
  3. stirringThe mixture was stirred at ambient temperature for 3 hours
  4. customAt the end of this time, the reaction mixture was partitioned between a saturated aqueous solution of sodium hydrogencarbonate and ethyl acetate
  5. washThe ethyl acetate layer was washed with a saturated aqueous solution of sodium chloride
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated by evaporation under reduced pressure
  8. customThe residue was purified by chromatography through a silica gel column
  9. additionby volume mixture of methylene chloride and ethyl acetate as the eluant

Sources & evidence

ORD record
ord-6ba8bb884177437ba6ae7b3258807e6a
Source dataset
uspto-grants-2001_12
Patent number
US06329405B1

Reaction notes

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