Sodium hydride → Methyl 2-(3-(cyclopropylmethyl)-2-oxoimidazolidin-1-yl)thiazole-5-carboxylate

온도

0 °C

To a solution of methyl 2-(2-oxoimidazolidin-1-yl)thiazole-5-carboxylate (0.50 g, 2.20 mmol) in N,N-dimethylformamide (15 mL) was added sodium hydride (0.084 g, 3.52 mmol, 60% in mineral oil) at 0° C. The reaction mixture was stirred at 0° C. for 0.5 hours, followed by the addition of (bromomethyl)cyclopropane (0.36 g, 2.64 mmol) and catalytic amount of tetra-n-butylammonium iodide. The reaction mixture was stirred at ambient temperature for 20 hours. The solvent was concentrated in vacuo, then diluted with ethyl acetate (200 mL) and washed with water (150 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluted with ethyl acetate/hexane (2/3) to afford the title compound as a colorless solid in 24% yield (0.15 g): mp 124-126° C. (ethyl acetate/hexanes); 1H NMR (300 MHz, CDCl3) δ 8.01 (s, 1H), 4.15-4.10 (m, 2H), 3.83 (s, 3H), 3.73-3.68 (m, 2H) 3.20 (d, J=7.1 Hz, 2H), 0.97-0.92 (m, 1H), 0.61-0.53 (m, 2H), 0.30-0.20 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 163.4, 162.6, 155.0, 145.2, 121.6, 52.0, 48.6, 42.2, 42.1, 8.9, 3.4; MS (ES+) m/z 282.2 (M+1).

1. stirringThe reaction mixture was stirred at ambient temperature for 20 hours
2. concentrationThe solvent was concentrated in vacuo
3. additiondiluted with ethyl acetate (200 mL)
4. washwashed with water (150 mL)
5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue was purified by column chromatography
9. washeluted with ethyl acetate/hexane (2/3)

ORD 기록

ord-54d19bb1921041ccb7eb2488d025b7d6

출처 데이터셋

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08293768B2