Water → HCID 86650027, compound

Temperature

0 °C

To a solution of N-(4-{2-[2-fluoro-4-(hydroxymethyl)phenyl]ethyl}-1,3-thiazol-2-yl)acetamide (194.7 mg, 0.665 mmol) in anhydrous dichloromethane (2 ml) were added triethylamine (0.17 ml, 1.20 mmol) and 4-dimethylaminopyridine (8.1 mg, 0.066 mmol), and the mixture was cooled to 0° C. Methanesulfonyl chloride (77 μl, 1.0 mmol) was added dropwise, and the mixture was stirred at room temperature for 1 hr. The mixture was cooled to 0° C., triethylamine (93 μl, 0.67 mmol) and methanesulfonyl chloride (51 μl, 0.67 mmol) were added, and the mixture was stirred at room temperature for 5 min. Iced water (2 ml) was added to the reaction mixture, and the mixture was stood still and partitioned. The aqueous layer was extracted 3 times with dichloromethane, and the combined organic layer was washed with 1M hydrochloric acid and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The concentrated residue was purified by silica gel column chromatography (Merck 9385 16 g, ethyl acetate:hexane=2:3) to give N-(4-{2-[4-(chloromethyl)-2-fluorophenyl]ethyl}-1,3-thiazol-2-yl)acetamide (59.6 mg, 0.191 mmol, yield 28.7%) as a pale-yellow solid.

1. temperatureThe mixture was cooled to 0° C.
2. stirringthe mixture was stirred at room temperature for 5 min
3. custompartitioned
4. extractionThe aqueous layer was extracted 3 times with dichloromethane
5. washthe combined organic layer was washed with 1M hydrochloric acid and saturated brine
6. dry with materialdried over anhydrous magnesium sulfate
7. concentrationconcentrated under reduced pressure
8. customThe concentrated residue was purified by silica gel column chromatography (Merck 9385 16 g, ethyl acetate:hexane=2:3)

ORD record

ord-12955fc69dd048d0845d120c5c11afa3

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08507690B2