2-Methyl-2-cyclopenten-1-one → 3-(3-Bromo-4-methoxyphenyl)-2-methylcyclopentanone

温度

0 °C

To a 100 mL RBF was added 2-bromo-4-iodo-1-methoxybenzene (0.59 g, 1.87 mmol), and 10 mL THF. iPrMgCl (0.94 mL, 1.89 mmol, 2M THF solution) was added at 0° C. via syringe. The reaction mixture was stirred at 0° C. for 1 hr. A solution of lithium 2-thenyl cyanocuprate (7.5 mL, 1.87 mmol) in THF was added, followed by 2-methylcyclopent-2-enone (150 mg, 1.56 mmol). The resulting reaction mixture was stirred at 0° C. for 1 hr and was allowed to warm up and stirred at rt for 1 hr. The reaction mixture was diluted with 30 mL EtOAc/hexane (1:1), washed with 30 mL 1N HCl, then 20 mL brine. Organics were dried over sodium sulfate, filtered and concentrated. Crude product was purified by silica gel chromatography to give 135 mg 3-(3-bromo-4-methoxyphenyl)-2-methylcyclopentanone as a mixture of two diastereomers at 1.6:1 ratio. 1H NMR for the major diastereomer (500 MHz, CDCl3): δ 7.35 (d, J=2.2 Hz, 1H), 7.05 (dd, J=2.2, 8.4 Hz, 1H), 6.89 (d, J=8.4 Hz, 1H), 3.92 (s, 3H), 3.55 (m, 1H), 2.2-2.6 (m, 5H), 0.83 (d, J=7.6 Hz, 3H). 1H NMR for the minor diastereomer (500 MHz, CDCl3): δ 7.48 (d, J=2.1 Hz, 1H), 7.19 (dd, J=2.2, 8.3 Hz, 1H), 6.93 (d, J=8.3 Hz, 1H), 3.94 (s, 3H), 2.75 (m, 1H), 2.2-2.6 (m, 5H), 1.07 (d, J=6.8 Hz, 3H).

1. customThe resulting reaction mixture
2. stirringwas stirred at 0° C. for 1 hr
3. temperatureto warm up
4. stirringstirred at rt for 1 hr
5. washwashed with 30 mL 1N HCl
6. dry with materialOrganics were dried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. customCrude product was purified by silica gel chromatography

ORDレコード

ord-b8a45243d276483a835f74509b7f3e6f

出典データセット

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09346825B2