反应详情

To a solution of 2,4-dibromobutanoyl chloride (10 g, 38 mmol) in 100 mL of DCM at 0° C. under nitrogen was added 3-fluoro-4-methylaniline (5.21 g, 42 mmol) followed by Et3N (6.3 mL, 45 mmol). The mixture was stirred at rt for 2 h, then concentrated in vacuo. The residue was dissolved in diethyl ether, then hexanes was added and a solid precipitated. The solid was removed by filtration and discarded. The filtrate was then concentrated in vacuo to give a dry residue. To a solution of this residue in 100 mL DMF at 0° C. under nitrogen was slowly added 60% NaH (1.82 g, 45 mmol). The mixture was stirred and allowed to warm up to rt over 30 min. The reaction mixture was slowly poured into 400 mL of icewater and allowed to stand overnight. A solid formed, and was filtered off and dried, then purified via silica gel chromatography eluting with 0-50% ethyl acetate/hexanes to give racemic 3-bromo-1-(3-fluoro-4-methylphenyl)pyrrolidin-2-one (5.6 g, 20.6 mmol). LCMS (method U) RT 3.41 min, m/z 273.97 (M+H+). 1H NMR (500 MHz, chloroform-d) δ 7.50 (dd, J=11.7, 2.2 Hz, 1H), 7.31-7.27 (m, 1H), 7.23-7.17 (m, 1H), 4.60 (dd, J=7.0, 2.9 Hz, 1H), 4.03 (ddd, J=9.8, 7.9, 6.8 Hz, 1H), 3.82 (ddd, J=10.0, 7.7, 2.7 Hz, 1H), 2.75 (dq, J=14.6, 7.5 Hz, 1H), 2.48 (ddt, J=14.3, 6.7, 2.7 Hz, 1H), 2.28 (d, J=1.7 Hz, 3H).

1. concentrationconcentrated in vacuo
2. dissolutionThe residue was dissolved in diethyl ether
3. additionhexanes was added
4. customa solid precipitated
5. customThe solid was removed by filtration
6. concentrationThe filtrate was then concentrated in vacuo
7. customto give a dry residue
8. customat 0° C.
9. stirringThe mixture was stirred
10. temperatureto warm up to rt over 30 min
11. additionThe reaction mixture was slowly poured into 400 mL of icewater
12. waitto stand overnight
13. customA solid formed
14. filtrationwas filtered off
15. customdried
16. custompurified via silica gel chromatography
17. washeluting with 0-50% ethyl acetate/hexanes