Sulfuric Acid → HCID 69156516, compound

HRID 750252Notes

Reaction equation

HRID 750252 reaction equation
[CH3:1][O:2][C:3]([C:5]1OC(=O)[C:8]2[C:13]([C:14]=1[C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=1)=[CH:12][C:11]([Cl:22])=[CH:10][CH:9]=2)=[O:4].[CH3:24][O:25]C(C1OC(=O)C2C(C=1C1C=CC(C)=CC=1)=CC=C(Cl)C=2)=O.Cl.[CH2:48]([O:50][C:51](=[O:55])[CH2:52][NH:53][NH2:54])C.C[O-].[Na+].S(=O)(=O)(O)O>CO>[CH3:1][O:2][C:3]([C:5]1[N:54]([NH:53][CH2:52][C:51]([O:50][CH3:48])=[O:55])[C:24](=[O:25])[C:8]2[C:13]([C:14]=1[C:15]1[CH:16]=[CH:17][C:18]([CH3:21])=[CH:19][CH:20]=1)=[CH:12][C:11]([Cl:22])=[CH:10][CH:9]=2)=[O:4]

Participants

7

Reactant 5

HCID 1118Sulfuric AcidHCID 10942334Sodium MethoxideHCID 11593468Acetic acid, 2-hydrazinyl-, ethyl ester, hydrochloride (1:1)HCID 69156376HCID 69156376, compoundHCID 69156599HCID 69156599, compound

Product 1

HCID 69156516HCID 69156516, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution (5.0 ml) of 6-chloro-1-oxo-4-(p-tolyl)-1H-isochromen-3-carboxylic acid methyl ester and 7-chloro-1-oxo-4-p-tolyl-1H-isochromen-3-carboxylic acid methyl ester (mixture, 270 mg) in methanol were added hydrazinoacetic acid ethyl ester hydrochloride (1.3 g) and sodium methoxide (0.44 g), and the mixture was heated under reflux for 2 hrs. After cooling the reaction mixture, conc. sulfuric acid (0.5 ml) was added to the reaction mixture, and the mixture was stirred at room temperature for 18 hrs. The solvent was removed under reduced pressure and the residue was partitioned between water and ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated. The residue was purified by medium pressure preparative LC (hexane/ethyl acetate=8/1-3/2) to give the title compound (85 mg) as colorless crystals. IR (KBr) cm−1: 1748, 1667, 1597, 1514, 1435, 1375, 1229. 1H-NMR (CDCl3) δ: 2.43 (3H, s), 3.62 (3H, s), 3.79 (3H, s), 3.96 (2H, d, J=6.2 Hz), 5.99 (1H, t, J=6.4 Hz), 7.14-7.38 (5H, m), 7.48 (1H, dd, J=2.0, 8.4 Hz), 8.40 (1H, d, J=8.4 Hz). HPLC analysis: purity 97% (4.44 min). MS (APCI+): 415 (M+H), 417.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 2 hrs
  3. additionwas added to the reaction mixture
  4. customThe solvent was removed under reduced pressure
  5. customthe residue was partitioned between water and ethyl acetate
  6. dry with materialThe organic layer was dried over magnesium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified by medium pressure preparative LC (hexane/ethyl acetate=8/1-3/2)

Sources & evidence

ORD record
ord-f47509f001fc480ab03bd76c0b628a84
Source dataset
uspto-grants-2008_07
Patent number
US07402595B2

Reaction notes

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