反应详情

温度

60 °C

To a stirred solution of Intermediate 2c (14.70 g, 58.27 mmol), Ph3P (30.56 g, 116.51 mmol) and Et3N (33 mL, 236.76 mmol) in THF (300 mL) at RT was added hexachloroethane (27.60 g, 116.58 mmol) during 10 min before then heating at 60° C. overnight. The cooled mixture was filtered and concentrated in vacuo to give a residual oil which was dissolved in DCM (200 mL) and extracted into dilute HCl (2M) until most product had been removed from the DCM phase by LCMS. These aqueous extracts were treated with solid NaOH (with cooling) to achieve ˜pH9 and extracted into DCM. Combined DCM extracts were washed with brine, dried (MgSO4), passed through a phase separation cartridge and concentrated in vacuo to give Intermediate 2d (11.30 g, 82%). LCMS (Method 3) Rt 2.99 min, m/z 235 [MH+]. 1H NMR (300 MHz, d6-d6-DMSO): 0.89 (3H, d, J 6.3), 1.40-1.88 (6H, m), 2.85-2.96 (1H, m), 3.18 (1H, dt, J 12.0, 4.5), 3.28-3.35 (1H, m), 7.42 (1H, ddd, J 10.0, 8.0, 2.3), 7.76 (1H, ddd, J 10.0, 4.9, 0.9), 8.31-8.35 (1H, m).

1. filtrationThe cooled mixture was filtered
2. concentrationconcentrated in vacuo
3. customto give a residual oil which
4. extractionextracted into dilute HCl (2M) until most product
5. customhad been removed from the DCM phase by LCMS
6. additionThese aqueous extracts were treated with solid NaOH (with cooling)
7. extractionextracted into DCM
8. washCombined DCM extracts were washed with brine
9. dry with materialdried (MgSO4)
10. custompassed through a phase separation cartridge
11. concentrationconcentrated in vacuo