Sodium hydride → ethyl rac-(2R,3S)-1-(4-methoxybenzyl)-2-methyl-5-oxopyrrolidine-3-carboxylate

Ethyl rac-(2R,3S)-2-methyl-5-oxopyrrolidine-3-carboxylate (30 g, 0.18 mol) in DMF (100 mL) was carefully added to a suspension of sodium hydride (7.6 g, 0.19 mol, 60% in mineral oil) in DMF (400 mL) at 0° C. The resulting mixture was stirred for 1 hour before 4-methoxybenzyl chloride (32.8 g, 28.5 mL, 0.21 mol) was added dropwise, followed by tert-butylammonium iodide (13 g, 35 mmol). The reaction mixture was stirred at room temperature for 10 hours and then quenched by adding saturated aqueous ammonium chloride solution (30 mL). The reaction mixture was diluted with water (100 mL) and extracted with ethyl acetate (500 mL×3). The combined organic layers were washed with brine (100 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford the crude product, which was purified by chromatography on silica gel (ethyl acetate/petroleum ether) to afford ethyl rac-(2R,3S)-1-(4-methoxybenzyl)-2-methyl-5-oxopyrrolidine-3-carboxylate. MS ESI calc'd. for C16H22NO4 [M+H]+ 292. found 292. 1H NMR (CDCl3, 400 MHz) δ: 7.13 (d, J=8.4 Hz, 2H), 6.82 (d, J=8.4 Hz, 2H), 4.91 (d, J=14.4 Hz, 1H), 4.08-4.15 (m, 2H), 3.89 (d, J=14.4 Hz, 1H), 3.76 (s, 3H), 3.62-3.63 (m, 1H), 2.71 (s, 3H), 1.18-1.26 (m, 6H).

1. additionwas added dropwise
2. customquenched
3. additionby adding saturated aqueous ammonium chloride solution (30 mL)
4. additionThe reaction mixture was diluted with water (100 mL)
5. extractionextracted with ethyl acetate (500 mL×3)
6. washThe combined organic layers were washed with brine (100 mL)
7. dry with materialdried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customto afford the crude product, which
11. customwas purified by chromatography on silica gel (ethyl acetate/petroleum ether)

ORDレコード

ord-c31036f516b24df386a9fa0188c606b7

出典データセット

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09242984B2