反应 #1244313

ord-ce58038345d343f0bc75ea678312300a

反应条件

详细条件
See reaction.notes.procedure_details.

后处理

  1. 1
    温度was heated
  2. 2
    温度to reflux for 2 h under an argon atmosphere
  3. 3
    温度The reagents were heated to 80° C. for one day and 120° C. for 2 hours under an argon atmosphere
  4. 4
    温度The mixture was cooled to room temperature
  5. 5
    workup.ADDITIONwas added (
  6. 6
    温度The mixture was heated to 100° C. for three days
  7. 7
    workup.ADDITIONwas added
  8. 8
    温度The mixture was heated to 100° C. for three days under an argon atmosphere
  9. 9
    温度cooled to room temperature
  10. 10
    洗涤The solution was washed with 1 N HCl (2×200 mL) and saturated sodium chloride
  11. 11
    干燥The organic layer was dried over MgSO4
  12. 12
    过滤filtered
  13. 13
    其他evaporated

实验过程

A mixture of ethyl (diethoxymethyl)phosphinate (21.7.0 g, 110 mmol) and 1,1,1,3,3,3-hexamethyldisilazane (23.3 mL, 110 mmol) was heated to reflux for 2 h under an argon atmosphere. The mixture was cooled to room temperature and a diastereomeric mixture ethyl 2-fluorobut-2-enoate (14.6 g, 110 mmol) was added. The reagents were heated to 80° C. for one day and 120° C. for 2 hours under an argon atmosphere. The mixture was cooled to room temperature and another portion of trimethylsilyl activated ethyl (diethoxymethyl)phosphinate was added (this had been prepared from ethyl (diethoxymethyl)phosphinate (21.7.0 g, 110 mmol) and 1,1,1,3,3,3-hexamethyldisilazane (23.3 mL, 110 mmol) in the same way as above). The mixture was heated to 100° C. for three days and still another portion of trimethylsilyl activated ethyl (diethoxymethyl)phosphinate was added. The mixture was heated to 100° C. for three days under an argon atmosphere, cooled to room temperature and then diluted with ethyl acetate (300 mL). The solution was washed with 1 N HCl (2×200 mL) and saturated sodium chloride. The organic layer was dried over MgSO4, filtered, and evaporated to give 42.0 g of a yellow oil. The residue was purified by chromatography on a wet-packed silica gel column eluting with methylene chloride and then with 98:2 methylene chloride/methanol. The appropriate fractions were combined and evaporated to give 3.6 g (10%) of ethyl 3-[(diethoxymethyl)(ethoxy)phosphoryl)]-2-fluorobutanoate as a clear oil. 1H NMR (400 MHz, CDCl3) δ 4.9-5.6 (m, 1H), 4.7-4.8 (m, 1H), 4.2-4.4 (m, 4H), 3.6-4.0 (m, 4H), 2.6-2.9 (m, 1H), 1.2-1.4 (m, 12H).

来源

DOI: 10.6084/m9.figshare.5104873.v1专利: US07807658B2uspto-grants-2010_10