N-bromobutanimide → 2-(3-bromo-2-oxopyrrolidin-1-yl)-N-(4-fluorobenzyl)-4-methylthiazole-5-carboxamide

Temperature

-78 °C

To a solution of N-(4-fluorobenzyl)-4-methyl-2-(2-oxopyrrolidin-1-yl)thiazole-5-carboxamide (0.35 g, 1.05 mmol) in anhydrous tetrahydrofuran (25 mL) at −78° C. was added lithium bis(trimethylsilyl)amide in tetrahydrofuran (2.31 mL, 2.31 mmol) dropwise. The reaction mixture was stirred at −78° C. for 5 minutes, followed by the addition of N-bromosuccinimide (0.19 g, 1.05 mmol) dropwise. The reaction mixture was stirred at −78° C. for 10 min, quenched with aqueous saturated ammonium chloride solution (10 mL) and extracted with dichloromethane (3×10 mL). The combined organic solutions were dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluting with ethyl acetate/hexanes (1/1) to afford the title compound as a white solid (0.22 g, 51%): 1H NMR (300 MHz, CDCl3) δ 7.34-7.24 (m, 2H), 7.07-6.97 (m, 2H), 5.98 (b s, 1H), 4.66-4.59 (m, 1H), 4.58 (d, J=5.8 Hz, 2H), 4.30-4.14 (m, 2H), 2.86-2.69 (m, 1H), 2.64 (s, 3H), 2.56-2.45 (m, 1H); MS (ES+) m/z 412 (M+1), 414 (M+1).

1. stirringThe reaction mixture was stirred at −78° C. for 10 min
2. customquenched with aqueous saturated ammonium chloride solution (10 mL)
3. extractionextracted with dichloromethane (3×10 mL)
4. dry with materialThe combined organic solutions were dried over anhydrous sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe residue was purified by column chromatography
8. washeluting with ethyl acetate/hexanes (1/1)

ORD record

ord-68f34e281c1c4c269ce4556280c862e6

Source dataset

uspto-grants-2012_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08236835B2