Hydrochloric Acid → 4-Oxo-4H, 5H-[1]benzopyrano [4,3-b]pyran-2-carboxylic Acid Methyl Ester

HRID 1439814Notes

Reaction equation

HRID 1439814 reaction equation
[CH2:1]([O:3][C:4](=[O:21])[C:5](=[O:20])[CH2:6][C:7]([CH:9]1[C:18](=O)[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[O:11][CH2:10]1)=[O:8])C.Cl>CO>[CH3:1][O:3][C:4]([C:5]1[O:20][C:18]2[C:17]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:11][CH2:10][C:9]=2[C:7](=[O:8])[CH:6]=1)=[O:21]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 12677755HCID 12677755, compound

Product 1

HCID 126777564-Oxo-4H, 5H-[1]benzopyrano [4,3-b]pyran-2-carboxylic Acid Methyl Ester

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 3-acetyl-4-chromanone (1.8 g, 9.5 mmoles, described in Example 5) in dry tetrahydrofuran (20 ml) is added dropwise to a suspension of 57% sodium hydride (1.17 g, 28.5 mmoles) in tetrahydrofuran (30 ml) and the mixture is heated at reflux temperature for 15 min. A solution of diethyl oxalate (1.39 g, 9.5 mmoles) is added dropwise under an atmosphere of nitrogen. The reaction mixture is heated at reflux temperature overnight and cooled to -40° C. A solution of 50% aqueous acetic acid (4 ml) is added and the reaction mixture evaporated. The residue is partitioned between chloroform and water, the organic phase is separated and the aqeuous phase is re-extracted with chloroform. The combined chloroform extracts are dried and evaporated. The residue is subjected to chromatography on silica gel. Elution with chloroform affords 4-(4-chromanon-3-yl)-2,4-dioxobutyric acid ethyl ester (VII; R1, R2, R3R4 and R17 = H, R19 = C2H5 and X = 0), which is crystallized from ether, m.p. 117°-119° C. b. Solid 3-acetyl-4-chromanone (0.570 g, 3 mmoles, described in Example 5) is added in portions at room temperature to a suspension of 57% sodium hydride (0.379 g, 9 mmoles) in dry tetrahydrofuran (10 ml). The mixture is heated within 15 min to 60° C and diethyl oxalate (0.438 g, 3 mmoles) in tetrahydrofuran (10 ml) is added. After heating at reflux temperature under an atmosphere of nitrogen for 17 hr., the solvent is removed under reduced pressure, the residue is dissolved in ice-water and extracted with ether. The aqeuous phase is acidified with 6N hydrochloric acid and extracted with chloroform. The organic phase is dried, evaporated, and the residue crystallized from methanol-chloroform to give 4-(4-chromanone-3-yl)-2,4-dioxobutyric acid (VI; R1, R2, R3, R4 and R5 = H, and X = 0), νmaxnujol 1705, 1615 and 1560 cm-1. c. A solution of 4-(4-chromanone-3-yl)-2,4-dioxobutyric acid ethyl ester [0.70 g, 2.4 mmoles, described above in (a)] in methanol is saturated with hydrogen chloride gas. The solution is heated at reflux temperature overnight and evaporated to dryness. The residue is chromatographed on silica gel using benzene-ethyl acetate (4:1). The eluate is evaporated and the residue is crystallized from chloroform-ether to give the title compound, m.p. 173°-174° C. d. In the same manner as described above in (c) but replacing 4(4-chromanone-3-yl)-2,4-dioxobutyric acid ethyl ester with an equivalent amount of the corresponding acid, 4-(4-chromanone-3-yl)-2,4-dioxobutric acid [described above in (b)], the title compound is obtained.

Workup

  1. temperatureThe solution is heated
  2. temperatureat reflux temperature overnight
  3. customevaporated to dryness
  4. customThe residue is chromatographed on silica gel
  5. customThe eluate is evaporated
  6. customthe residue is crystallized from chloroform-ether

Sources & evidence

ORD record
ord-6c75837f477f4daa8947fd6488352269
Source dataset
uspto-grants-1977_11
Patent number
US04060619

Reaction notes

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