Hydrochloric Acid → Ethyl 7-amino-4-oxo-4H-chromene-2-carboxylate

HRID 1376567Notes

Reaction equation

HRID 1376567 reaction equation
[C:1]([C:4]1[CH:9]=[CH:8][C:7]([NH:10]C(=O)C)=[CH:6][C:5]=1[OH:14])(=[O:3])[CH3:2].[C:15](OCC)(=O)[C:16]([O:18][CH2:19][CH3:20])=[O:17].[O-]CC.[Na+].Cl>C(O)C.C(Cl)Cl.O>[NH2:10][C:7]1[CH:8]=[CH:9][C:4]2[C:1](=[O:3])[CH:2]=[C:15]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[O:14][C:5]=2[CH:6]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 7268Diethyl OxalateHCID 2723922Sodium ethoxideHCID 2775185N-(4-acetyl-3-hydroxyphenyl)acetamide

Product 1

HCID 10728325Ethyl 7-amino-4-oxo-4H-chromene-2-carboxylateYield 75.6%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of N-[4-acetyl-3-hydroxyphenyl)acetamide (24.1 g, 0.125 mol) and diethyl oxalate (47.5 g, 0.33 mol) in absolute ethanol (200 mL) was added to a solution of sodium ethoxide (14 g sodium in 300 mL absolute ethanol). The reaction was heated to reflux for 2 hours and allowed to cool to room temperature then poured into water (500 mL) and methylene chloride (1500 mL). The aqueous layer was made slightly acidic using 6N hydrochloric acid. The organic layer separated and the aqueous layer washed again using methylene chloride (500 mL). The combined organic layers were dried over anhydrous magnesium sulfate, filtered, and the solvent removed under vacuum. The solid material (35.8 g) was dissolved in ethanol (350 mL) and concentrated hydrochloric acid (6 mL) was added. The solution was heated to reflux for 1 day, removed from heat and allowed to stand for 2 days. The orange solid was filtered to afford 17 g of ethyl 7-amino-4-oxo-4H-1-benzopyran-2-carboxylate. The mother liquor was concentrated to afford another 4.94 g of desired product. Yield 75.6%, 1H NMR (DMSO-d6) δ 1.32 (3H, t, J=7.25 Hz, CH2CH3,), 4.34 (2H, q, J=7.03 Hz, CH2CH3), 6.50 (2H, bs, NH2), 6.53 (1H, d, J=1.98 Hz, =CH), 6.69 (1H, dd, J=8.78, 1.98 Hz, ArH), 6.71 (1H, s, ArH), 7.68 (1H, d, J=8.78 Hz, ArH); MS (EI) m/z, 233 (M+).

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux for 2 hours
  3. customThe organic layer separated
  4. washthe aqueous layer washed again using methylene chloride (500 mL)
  5. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. customthe solvent removed under vacuum
  8. dissolutionThe solid material (35.8 g) was dissolved in ethanol (350 mL)
  9. additionconcentrated hydrochloric acid (6 mL) was added
  10. temperatureThe solution was heated
  11. temperatureto reflux for 1 day
  12. customremoved
  13. temperaturefrom heat
  14. filtrationThe orange solid was filtered

Sources & evidence

ORD record
ord-1da994dfdf584d789d0232c7567671f3
Source dataset
uspto-grants-1997_09
Patent number
US05663194

Reaction notes

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