diethyl 2,2,3,3,4,4-hexafluoropentanedioate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Dissolve 3.4 mmol of benzylamine in 12 mL of methylene chloride and cool in an ice/water bath under argon. Add 4.1 mmol of trimethylaluminum as a 2 M hexane solution dropwise during several minutes. Stir for 10 min, then add 3.4 mmol of the product of Example 7 as a solution in 4 mL of methylene chloride. Remove ice bath and stir for 2 h at room temperature, then heat under reflux for 3 h. Cool in an ice/water bath and cautiously decompose excess trimethylaluminum with water. Partition the reaction mixture between 30 mL each of ether and water and wash the organic layer with 1N HCl, saturated sodium bicarbonate, and brine, then dry over MgSO4 and concentrate in vacuo. Dissolve the residue in 2 mL of DMF and add to a slurry of 3.5 mmol of sodium hydride (washed with hexane twice to remove mineral oil) and 4 mL of DMF under argon. Stir for 16 h at room temperature. Cautiously decompose excess sodium hydride with several drops of water and partition the mixture between ethyl acetate and water. Extract the aqueous layer twice with more ethyl acetate, then wash the combined organic layers with 1N HCl, saturated sodium bicarbonate, and brine. Dry over MgSO4 and concentrate in vacuo. Purify the residue by silica gel chromatography using ethyl acetate/hexanes eluant to yield the title compound. cool in an ice/water bath under argon Remove ice bath and stir for 2 h at room temperature heat under reflux for 3 h Cool in an ice/water bath Partition the reaction mixture between 30 mL each of ether and water wash the organic layer with 1N HCl, saturated sodium bicarbonate, and brine dry over MgSO4 concentrate in vacuo Dissolve the residue in 2 mL of DMF washed with hexane twice to remove mineral oil) and 4 mL of DMF under argon Stir for 16 h at room temperature Cautiously decompose excess sodium hydride with several drops of water and partition the mixture between ethyl acetate and water Extract the aqueous layer twice with more ethyl acetate wash the combined organic layers with 1N HCl, saturated sodium bicarbonate, and brine Dry over MgSO4 concentrate in vacuo Purify the residue by silica gel chromatography

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 30.3 g. (0.015 mol.) of Vitride (70% in benzene) in 30 ml. of dry tetrahydrofuran (THF) was added dropwise over 45 min. to a stirred solution of 25.0 g. (0.084 mol.) of diethyl perfluoroglutarate in 200 ml. of THF at -70° C. The mixture was stirred for an additional 2 hours at -70° C. followed by decomposing the Vitride as described in Example 1 to give 16.8 g. (87% by weight) of the title compound as a pale yellow liquid. Distillation afforded a colorless oil: boiling range 65°-70° C. (1.7 mm); nD26 1.3671; νmaxneat 3350 (broad) cm-1 ; nmr (CDCl3) δ 1.20 (t,3H,J=6.5 Hz), 3.46-4.10 (m,2H,J=4 Hz) 5.07-5.26 (m,2H), 8.33 (bd s, 1H, exch.) which on prolonged storage (1 month) solidified to a white crystalline product; melting range 84°-6° C. (C6H6). at -70° C to give 16.8 g