Hydrochloric Acid → 3-cyclopentyl-2(R)-(4-methanesulfonyl-phenyl)-N-(4-methyl-thiazol-2-yl)-propionamide

Temperature

0 °C

A solution of triphenylphosphine (345 mg, 1.31 mmol) in methylene chloride (4 mL) was cooled to 0° C. and then treated with N-bromosuccinimide (234 mg, 1.31 mmol). The reaction mixture was stirred at 0° C. for 15 min and then treated with 3-cyclopentyl-2(R)-(4-methanesulfonylphenyl)propionic acid (300 mg, 1.01 mmol). The resulting reaction mixture was stirred at 0° C. for 5 min and then allowed to warm to 25° C. where it was stirred for 25 min. The reaction mixture was then treated with 2-amino-4-methylthiazole (288 mg, 2.52 mmol). The resulting reaction mixture was allowed to stir at 25° C. for 20 h. The reaction mixture was then diluted with water (30 mL), a 1N aqueous hydrochloric acid solution (5 mL), and ethyl acetate (30 mL). The layers were separated, and the organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 1/1 hexanes/ethyl acetate) afforded 3-cyclopentyl-2(R)-(4-methanesulfonyl-phenyl)-N-(4-methyl-thiazol-2-yl)-propionamide (192 mg, 48%) as an off-white foam: mp 83-87° C. (foam to gel); [α]23589=−35.7° (c=1.01, chloroform); EI-HRMS m/e calcd for C19H24N2O3S2 (M+) 392.1228, found 392.1227.

1. customThe resulting reaction mixture
2. stirringwas stirred at 0° C. for 5 min
3. temperatureto warm to 25° C. where it
4. stirringwas stirred for 25 min
5. customThe resulting reaction mixture
6. stirringto stir at 25° C. for 20 h
7. customThe layers were separated
8. dry with materialthe organic layer was dried over magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo

ORD record

ord-a052edeb5a4d46b490b11e89d71c90d8

Source dataset

uspto-grants-2003_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06610846B1