Acetic Anhydride → Acetic acid 3-[2-(3,4-dichloro-phenyl)-2-(thiazol-2-ylcarbamoyl)-ethyl]-cyclopentyl ester

A solution of 2-(3,4-dichloro-phenyl)-3-(3-hydroxy-cyclopentyl)-N-thiazol-2-yl-propionamide (prepared as in Example 36, 147.8 mg, 0.38 mmol) and acetic anhydride (72 μL, 0.77 mmol) in pyridine (2 mL) and methylene chloride (1 mL) was stirred at 25° C. for 20 h. The resulting reaction mixture was concentrated in vacuo. Since the reaction did not go to completion, the residue was re-dissolved in pyridine (1.8 mL) and acetic anhydride (1.4 mL, 14.84 mmol) and then stirred at 25° C. for an additional 7 h. The reaction mixture was concentrated in vacuo and then diluted with ethyl acetate (50 mL). The organic layer was washed with a 1N aqueous hydrochloric acid solution (3×50 mL), water (50 mL), and a saturated aqueous sodium chloride solution (50 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 35% ethyl acetate/hexanes) afforded acetic acid 3-[2-(3,4-dichloro-phenyl)-2-(thiazol-2-ylcarbamoyl)-ethyl]-cyclopentyl ester (80.8 mg, 49%) as a white solid: mp 49–52° C.; (ES)+-HRMS m/e calcd for C19H20Cl2N2O3S (M+H)+ 427.0645 found 427.0648.

1. customThe resulting reaction mixture
2. concentrationwas concentrated in vacuo
3. dissolutionthe residue was re-dissolved in pyridine (1.8 mL)
4. concentrationThe reaction mixture was concentrated in vacuo
5. additiondiluted with ethyl acetate (50 mL)
6. washThe organic layer was washed with a 1N aqueous hydrochloric acid solution (3×50 mL), water (50 mL)
7. dry with materiala saturated aqueous sodium chloride solution (50 mL), dried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated in vacuo

ORD record

ord-bc325c87d81e4aafba79a8ccbbb088c1

Source dataset

uspto-grants-2006_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07105671B2