Potassium Carbonate → rac-6-acetyl-7-[5-[(3,4-dihydro-4-oxo-8-propyl-2H-1-benzopyran-7-yl)oxy]pentyloxy]-3,4-dihydro-2H-1-benzopyran-2-carboxylic acid methyl ester

HRID 327937Notes

Reaction equation

HRID 327937 reaction equation
[OH:1][C:2]1[CH:12]=[CH:11][C:5]2[C:6](=[O:10])[CH2:7][CH2:8][O:9][C:4]=2[C:3]=1[CH2:13][CH2:14][CH3:15].[CH3:16][O:17][C:18]([CH:20]1[CH2:25][CH2:24][C:23]2[CH:26]=[C:27]([C:41](=[O:43])[CH3:42])[C:28]([O:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35]OS(C)(=O)=O)=[CH:29][C:22]=2[O:21]1)=[O:19].C(=O)([O-])[O-].[K+].[K+]>CCOCC.C1(C)C=CC=CC=1.COCCOCCN(CCOCCOC)CCOCCOC>[CH3:16][O:17][C:18]([CH:20]1[CH2:25][CH2:24][C:23]2[CH:26]=[C:27]([C:41](=[O:43])[CH3:42])[C:28]([O:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][O:1][C:2]3[CH:12]=[CH:11][C:5]4[C:6](=[O:10])[CH2:7][CH2:8][O:9][C:4]=4[C:3]=3[CH2:13][CH2:14][CH3:15])=[CH:29][C:22]=2[O:21]1)=[O:19]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 111441396-Acetyl-3,4-dihydro-7-[[5-[(methylsulfonyl)oxy]pentyl]oxy]-2h-1-benzopyran-2-carboxylic acid methyl esterHCID 153182992,3-dihydro-7-hydroxy-8-propyl-4H-1-benzopyran-4-one

Product 1

HCID 54190726rac-6-acetyl-7-[5-[(3,4-dihydro-4-oxo-8-propyl-2H-1-benzopyran-7-yl)oxy]pentyloxy]-3,4-dihydro-2H-1-benzopyran-2-carboxylic acid methyl esterYield 91%

Reagents, catalysts & solvents 3

HCID 112414Ethanamine, 2-(2-methoxyethoxy)-N,N-bis[2-(2-methoxyethoxy)ethyl]-CatalystHCID 1140TolueneSolvent2×HCID 3283Diethyl EtherSolvent

Procedure

A mixture of 0.8 g (3.88 mmol) of 2,3-dihydro-7-hydroxy-8-propyl-4H-1-benzopyran-4-one, 1.6 g (3.88 mmol) of rac-6-acetyl-7-[[5-[(methylsulfonyl)oxy]pentyl]oxy]-3,4-dihydro-2H-1-benzopyran-2-carboxylic acid methyl ester, 0.78 g (5.65 mmol) of anhydrous potassium carbonate, 0.082 g of tris[2-(2-methoxyethoxy)ethyl]amine (TDA-1), and 20 mL of toluene was stirred and refluxed for 6 hr. After being cooled, the reaction mixture was diluted with ether and toluene and filtered with suction. The solids were washed with more toluene and ether and then the filtrate and washes were combined and concentrated in vacuo. The residue was dissolved in 1:1 ether-dichloromethane and washed with water and brine. Completion of the usual work-up afforded a solid residue which was purified by flash chromatography, eluting with 1:1 hexane-ethyl acetate. There was obtained 1.85 g (91%) of rac-6-acetyl-7-[5-[(3,4-dihydro-4-oxo- 8-propyl-2H-1-benzopyran-7-yl)oxy]pentyloxy]-3,4-dihydro-2H-1-benzopyran-2-carboxylic acid methyl ester as a solid, mp 131°-133° C. This material was saponified using the procedure described in example 8 giving rac-6-acetyl-7-[5-[3,4-dihydro-4-oxo-8-propyl-2H-1-benzopyran-7-yl)oxy]pentyloxy]-3,4-dihydro-2H-1-benzopyran-2-carboxylic acid as an off-white solid, mp 148°-151° C., in 38.4% yield, after recrystallization from hexane ethyl acetate.

Workup

  1. temperaturerefluxed for 6 hr
  2. temperatureAfter being cooled
  3. filtrationfiltered with suction
  4. washThe solids were washed with more toluene and ether
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue was dissolved in 1:1 ether-dichloromethane
  7. washwashed with water and brine
  8. customCompletion of the usual work-up afforded a solid residue which
  9. customwas purified by flash chromatography
  10. washeluting with 1:1 hexane-ethyl acetate

Sources & evidence

ORD record
ord-fe8470441d8141399fc164542a6048c5
Source dataset
uspto-grants-1993_12
Patent number
US05273999

Reaction notes

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