Citric Acid → (3-{3-[2-(4-Methylbenzoyl)-1h-pyrrol-1-yl]-1-propynyl}phenoxy)acetic acid

To a solution of the compound (537 mg, 2.05 mmol) of Example 22-2 in tetrahydrofuran (8.0 ml) were added under ice cooling triethylamine (0.420 ml, 3.00 mmol) and methanesulfonyl chloride (0.170 ml, 2.20 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 a 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 (4.0 ml). Thereto was added lithium bromide (500 mg, 5.80 mmol) and the mixture was stirred for 1 hour. 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 (259 mg, 1.40 mmol) of Reference example 1 and potassium t-butoxide (157 mg, 1.40 mmol) in tetrahydrofuran (4 ml) under ice cooling. The mixture was stirred for 7 hours under ice cooling. Thereto were added methanol (2.0 ml) and an aqueous 4N sodium hydroxide solution (2.0 ml) and the mixture was stirred for 2 hours at room temperature. The reaction mixture was washed with hexane and the precipitate was taken by filtration. The precipitate was washed with a mixture of hexane and ether (1:1) and dried under reduced pressure to give the subject compound (529 mg, 95%) as white crystals.

1. extractionthe mixture was extracted with ethyl acetate
2. washThe organic layer was washed with cold 10% aqueous citric acid solution
3. dry with materiala cold aqueous saturated sodium hydrogencarbonate solution in the order and dried over sodium sulfate
4. customThe solvent was removed
5. dissolutionthe residue was dissolve in tetrahydrofuran (4.0 ml)
6. stirringthe mixture was stirred for 1 hour
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 7 hours under ice cooling
13. washThe reaction mixture was washed with hexane
14. filtrationthe precipitate was taken by filtration
15. washThe precipitate was washed with a mixture of hexane and ether (1:1)
16. customdried under reduced pressure

ORD record

ord-8eaa1d312c1745bd9c3f537dd8fcd922

Source dataset

uspto-grants-2007_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07220773B2