反应详情

温度

0 °C

Iodomethane (0.314 mL, 5.04 mmol, 1.1 equiv) and sodium hydride (60% in mineral oil, 202 mg, 5.04 mmol, 1.1 equiv) were combined in DMF (10 mL) and cooled to 0° C. The product of Step (b) (1.275 g, 4.59 mmol, 1 equiv) was added slowly as a solution in DMF (11 mL). Following the addition, the reaction was warmed to room temperature and stirred for two hours. The reaction mixture was diluted with water and poured into EtOAc. The phases were separated and the aqueous phase was extracted with an additional portion of EtOAc. The combined organic phases were washed with water, 15% aq. Na2S2O4, and satd. NaCl, then dried over sodium sulfate. The suspension was filtered and the filtrate was concentrated en vacuo to afford a mixture of two regioisomeric products. The isomers were separated by flash chromatography (3→5% Et2O/CH2Cl2), and regiochemistry of the desired product was confirmed by NOE analysis. 550 mg (41%) of the title compound was isolated as a yellow solid. 1H NMR (400 MHz, CDCl3) 7.30-7.27 (m, 2H), 7.02-6.97 (m, 2H), 5.21 (s, 1H), 3.91 (s, 3H), 3.63 (s, 3H), 2.84 (s, 3H), 2.38 (s, 3H).

1. additionthe addition
2. temperaturethe reaction was warmed to room temperature
3. customThe phases were separated
4. extractionthe aqueous phase was extracted with an additional portion of EtOAc
5. washThe combined organic phases were washed with water, 15% aq. Na2S2O4
6. dry with materialNaCl, then dried over sodium sulfate
7. filtrationThe suspension was filtered
8. concentrationthe filtrate was concentrated en vacuo
9. customto afford
10. additiona mixture of two regioisomeric products
11. customThe isomers were separated by flash chromatography (3→5% Et2O/CH2Cl2), and regiochemistry of the desired product