Sulfuric Acid → 5-[(3-Carboxyphenyl)carbonyl]-2-[6-[(3,4-dihydro-4-oxo-8-propyl-2H-1-benzopyran-7-yl)oxy]hexyloxy]benzenepropanoic Acid

HRID 1647987Notes

Reaction equation

HRID 1647987 reaction equation
C([O:3][C:4](=[O:48])[CH2:5][CH2:6][C:7]1[CH:12]=[C:11]([C:13]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([O:23]CC)=[O:22])[CH:16]=2)=[O:14])[CH:10]=[CH:9][C:8]=1[O:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][O:33][C:34]1[CH:44]=[CH:43][C:37]2[C:38](=[O:42])[CH2:39][CH2:40][O:41][C:36]=2[C:35]=1[CH2:45][CH2:46][CH3:47])C.O.[OH-].[Li+].S(=O)(=O)(O)O.C(OCC)(=O)C>C1COCC1.O>[C:21]([C:17]1[CH:16]=[C:15]([C:13]([C:11]2[CH:10]=[CH:9][C:8]([O:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][O:33][C:34]3[CH:44]=[CH:43][C:37]4[C:38](=[O:42])[CH2:39][CH2:40][O:41][C:36]=4[C:35]=3[CH2:45][CH2:46][CH3:47])=[C:7]([CH2:6][CH2:5][C:4]([OH:48])=[O:3])[CH:12]=2)=[O:14])[CH:20]=[CH:19][CH:18]=1)([OH:23])=[O:22]

Participants

7

Reactant 4

HCID 1118Sulfuric AcidHCID 8857Ethyl AcetateHCID 168937Lithium hydroxide, monohydrateHCID 536732502-[6-[(2,3-dihydro-4-oxo-8-propyl-4H-1-benzopyran-7-yl)oxy]hexyloxy]-5-[[3-(ethoxycarbonyl)phenyl]carbonyl]benzenepropanoic acid ethyl ester

Product 1

HCID 199220415-[(3-Carboxyphenyl)carbonyl]-2-[6-[(3,4-dihydro-4-oxo-8-propyl-2H-1-benzopyran-7-yl)oxy]hexyloxy]benzenepropanoic Acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 0.144 g (0.70 mmol) of 2,3-dihydro-7-hydroxy-8-propyl-4H-1-benzopyran-4-one, 0.371 g (0.70 mmol) of 2-[(6-bromohexyl)oxy]-5-[[3-(ethoxycarbonyl)phenyl]carbonyl]benzenepropanoic acid ethyl ester, 0.479 g (3.47 mmol) of anhydrous granular potassium carbonate and 13.1 mL of 2-butanone was stirred and refluxed for 18 hr. The resulting slurry was filtered with suction and the solids washed thoroughly with ethyl acetate. The filtrate and washes were combined and concentrated in vacuo and the residue was purified by flash chromatography on 75 g of silica gel, eluting with 3:1 hexane-ethyl acetate, giving 0.37 g (80.6%) of 2-[6-[(2,3-dihydro-4-oxo-8-propyl-4H-1-benzopyran-7-yl)oxy]hexyloxy]-5-[[3-(ethoxycarbonyl)phenyl]carbonyl]benzenepropanoic acid ethyl ester as a white solid, mp 58°-59.5° C. A mixture of 0.331 g (0.50 mmol) of this ester in 6 mL of THF and 6 mL of water was treated with 64.7 mg (1.54 mmol) of lithium hydroxide monohydrate and the resulting mixture was stirred for 25.5 hr at room temperature, before being acidified with 17 mL of 3N aqueous sulfuric acid. Work-up with ethyl acetate in the usual manner gave a crude product which was recrystallized from hexane-ethyl acetate affording 0.242 g (79.7%) of the title compound as a white solid, mp 169°-172° C.

Sources & evidence

ORD record
ord-ce3a7bb0067d4b67a6c9dc0b2d21d9c1
Source dataset
uspto-grants-1995_07
Patent number
US05434186

Reaction notes

Loading…