Citric Acid → (2-Chloro-5-{(1e)-3-[2-(4-methylbenzoyl)-1h-pyrrol-1-yl]-1-propenyl}phenoxy)acetic acid

To a solution of the compound (299 mg, 1.00 mmol) of Example 20-4 in tetrahydrofuran (4.0 ml) were added under ice cooling triethylamine (0.210 ml, 1.50 mmol) and methanesulfonyl chloride (0.085 ml, 1.10 mmol) in the order. The mixture was stirred for 1 hour under ice cooling. To the reaction mixture were added cold 10% aqueous citric acid solution and the mixture was extracted with ethyl acetate. The organic layer was washed with cold 10% aqueous citric acid solution and cold aqueous saturated sodium hydrogencarbonate solution in the order and dried over sodium sulfate. The solvent was removed and the residue was dissolve in tetrahydrofuran (2.0 ml). Thereto was added lithium bromide (174 mg, 2.00 mmol) and the mixture was stirred for 3 hours. To the reaction mixture was added water and the mixture was extracted with ethyl acetate. The organic layer was washed with water and an aqueous saturated sodium chloride solution and dried over sodium sulfate. The solvent was removed and the residue was dissolved in tetrahydrofuran (2 ml). The solution was dropped into a solution of the compound (185 mg, 1.00 mmol) of Reference example 1 and potassium t-butoxide (112 mg, 1.00 mmol) in tetrahydrofuran (2 ml) under ice cooling. The mixture was stirred for 5 hours under ice cooling. Thereto were added methanol (2.0 ml) and an aqueous IN sodium hydroxide solution (2.0 ml) and the mixture was stirred for 2 hours. The reaction mixture was washed with hexane and ether and acidified with potassium hydrogensulfate, and extracted with chloroform. The organic layer was washed with an aqueous saturated sodium chloride solution and dried over sodium sulfate. The solvent was removed to give the subject compound as brown crystals (281 mg, 60%).

1. extractionthe mixture was extracted with ethyl acetate
2. washThe organic layer was washed with cold 10% aqueous citric acid solution and cold aqueous saturated sodium hydrogencarbonate solution in the order
3. dry with materialdried over sodium sulfate
4. customThe solvent was removed
5. dissolutionthe residue was dissolve in tetrahydrofuran (2.0 ml)
6. stirringthe mixture was stirred for 3 hours
7. extractionthe mixture was extracted with ethyl acetate
8. washThe organic layer was washed with water
9. dry with materialan aqueous saturated sodium chloride solution and dried over sodium sulfate
10. customThe solvent was removed
11. dissolutionthe residue was dissolved in tetrahydrofuran (2 ml)
12. stirringThe mixture was stirred for 5 hours under ice cooling
13. washThe reaction mixture was washed with hexane and ether
14. extractionextracted with chloroform
15. washThe organic layer was washed with an aqueous saturated sodium chloride solution
16. dry with materialdried over sodium sulfate
17. customThe solvent was removed

ORD record

ord-f3e66f7ca26c4dfe8396cd0e8550debc

Source dataset

uspto-grants-2007_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07220773B2