Water → HCID 19972516, compound

HRID 1452339Notes

Reaction equation

HRID 1452339 reaction equation
[CH3:1][C:2]1[C:7](=[O:8])[C:6]2[CH:9]=[CH:10][CH:11]=[C:12]([C:13]([O:15]C)=[O:14])[C:5]=2[O:4][C:3]=1[C:17]1[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=1.O1CCOCC1.[OH-].[Na+].O>CO>[CH3:1][C:2]1[C:7](=[O:8])[C:6]2[CH:9]=[CH:10][CH:11]=[C:12]([C:13]([OH:15])=[O:14])[C:5]=2[O:4][C:3]=1[C:17]1[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=1

Participants

6

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 312751,4-DioxaneHCID 19972375HCID 19972375, compound

Product 1

HCID 19972516HCID 19972516, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 6.2 g of methyl 3-propionylsalicylate and 5.8 g of nicotinoyl chloride hydrochloride in 18 ml of anhydrous pyridine was stirred and heated at 100° C. for 2 hours under nitrogen. After that, 16 ml of triethylamine was added and heating was continued for 1 hour at the same temperature. The reaction mixture was cooled to room temperature, poured into 600 ml of water and the precipitate was collected by suction and washed with water, yielding 5.4 g of methyl 2-hydroxy-3-(2-nicotinoyl)propionylbenzoate, which was used without purification in the next step. 3.4 g of this Intermediate was heated at 100° C. for 1.5 hours after dissolution in a mixture containing 15 ml of acetic acid and 1 ml of 37% hydrochloric acid. After cooling to room temperature, the mixture was poured into 150 ml of water and extracted with ethyl acetate. The organic phase was washed with 5% aqueous sodium hydrogen carbonate solution, followed by water, dried on sodium sulfate and evaporated in vacuo, yielding 1.3 g of crude methyl 3-methyl-4-oxo-2-(3-pyridyl)-4H-1-benzopyran-8-carboxylate. 1 g of the above ester was dissolved in 9 ml of methanol and 15 ml of 1,4-dioxane and slowly added with 1.7 ml of 10N sodium hydroxide, maintaining the temperature between 20 and 25° C. After 1 hour at 50° C., the reaction mixture was poured into 150 ml of water and extracted with ethyl acetate. The aqueous layer was acidified with in aqueous hydrochloric acid solution. The precipitate was collected by suction, yielding 0.6 g of 3-methyl-4-oxo-2-(3-pyridyl)-4H-1-benzopyran-8-carboxylic acid, which was used without purification in the next step. The title compound was prepared according to Example 86, but using the above Intermediate instead of 4-oxo-2-phenyl-4H-1- benzopyran-8-carboxylic acid and carrying out the reaction for 2 hours at room temperature. The base was purified by flash chromatography on silica gel eluting with a mixture of chloroform-methanol (98:2), followed by crystallization from acetone, yielding 0.15 g (m.p. 134.5°-137° C.).

Workup

  1. temperaturemaintaining the temperature between 20 and 25° C
  2. extractionextracted with ethyl acetate
  3. customThe precipitate was collected by suction

Sources & evidence

ORD record
ord-775115de9cde48e28ead45f5a1d0fd2e
Source dataset
uspto-grants-1997_02
Patent number
US05605896

Reaction notes

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