反应详情

温度

-25 °C

All glassware was dried prior to use. THF was dried over molecular sieves. LiCl was dried at 150° C. for 1 h, then stored in a closed bottle. All reaction solutions were made under nitrogen, and the solutions were transferred via syringe. 4-Iodobenzoic acid tert-butyl ester (3 g, 9.9 mmol) was dissolved in THF (7.5 ml), and cooled to −20 to −30° C. Isopropyl magnesium chloride (10.9 mmol, 2M in THF) was added over 5 min, and the solution was stirred for 30 min. A solution of CuCN (0.97 g, 10.9 mmol) and LiCl (0.92 g, 21.7 mmol) in 7.5 ml THF was added. The reaction was removed from the cold bath and allowed to warm to rt. After 15 min, trimethylphosphite (0.62 ml) was added. After stirring for 5 min—iodododecanoic acid methyl ester (2.69 g, 7.89 mmol) was added in a solution of THF (5 ml). After stirring for 16 h, the reaction was quenched with sat. NH4Cl (6 ml). Water (100 ml) was added and the solution was extracted with AcOEt (3×100 ml). The organic extracts were pooled ant washed with water (100 ml) (some sat. NaCl and MeOH was added to aid phase separation) and sat. NaCl (100 ml), dried over MgSO4 and concentrated under vacuum to yield a two-phased residue (5.85 g). The residue was dissolved in AcOEt and added drop wise to a bed of silica in a glass filter (7.5 cm dia×3 cm). 200 ml of AcOEt was washed through the silica, and the filtrate was concentrated to yield a residue. This was dissolved in DCM (10 ml) and purified by flash chromatography (15 cm×40 mm, eluant 9:1 heptane/AcOEt). The relevant fractions were pooled and concentrated under vacuum. This was dissolved in 9:1 heptane/AcOEt (7 ml) and purified again by flash chromatography (15 cm×40 mm, eluant 9:1 heptane/AcOEt) to yield a colorless oil (185 mg).

1. customAll glassware was dried
2. dry with materialTHF was dried over molecular sieves
3. dry with materialLiCl was dried at 150° C. for 1 h
4. customthe solutions were transferred via syringe
5. customThe reaction was removed from the cold bath
6. temperatureto warm to rt
7. waitAfter 15 min
8. additiontrimethylphosphite (0.62 ml) was added
9. stirringAfter stirring for 16 h
10. customthe reaction was quenched with sat. NH4Cl (6 ml)
11. additionWater (100 ml) was added
12. extractionthe solution was extracted with AcOEt (3×100 ml)
13. washThe organic extracts were pooled ant washed with water (100 ml) (some sat. NaCl and MeOH
14. additionwas added
15. customphase separation) and sat. NaCl (100 ml)
16. dry with materialdried over MgSO4
17. concentrationconcentrated under vacuum