Tetrahydrofuran → Triphenylphosphine Oxide

Participants

Reaction Steps

A flame-dried flask is charged with N-(4-chlorobenzyl)-4-hydroxy-6-(4-morpholinylmethyl)-3-quinolinecarbothioamide (0.060 g) from Preparation No. 47, triphenylphosphine (0.045 g), and freshly distilled THF (1.5 mL). To this solution is added methanol (8.00 μL) and diethyl azodicarboxylate (28.00 μL). The reaction is stirred at room temperature for 18 h. Monitoring of the reaction still shows a significant amount of starting material left. Additional PPh3 (0.025 g), methanol (5.00 μL), and diethyl azodicarboxylate (14.00 μL) are added and the reaction is stirred for 18 h. Since monitoring of the reaction still shows some starting material, 10 equivalents each of PPh3, methanol, and diethyl azodicarboxylate are added. A reasonable exotherm is seen after adding diethyl azodicarboxylate. The reaction is immediately monitored by TLC and starting material is consumed. The solvents are removed and the residue is dissolved in CH2Cl2/MeOH and adsorbed onto silica. Purification by column chromatography (eluent CH2Cl2 (1 L), 1% MeOH:CH2Cl2 (1 L), 2% MeOH:CH2Cl2 (2 L), 4% MeOH:CH2Cl2 (1 L), 7% MeOH:CH2Cl2 (1 L)) affords the title compound contaminated with triphenylphosphine oxide. These fractions are combined and concentrated and the residue is again adsorbed onto silica. Purification by a second chromatography (eluent 1:1 hexanes:ethyl acetate (1 L), 45:55 hexanes:ethyl acetate (1 L), 4:6 hexanes:ethyl acetate (1 L), 35:65 hexanes:ethyl acetate (1 L), 1:3 hexanes:ethyl acetate (1 L), 2:8 hexanes:ethyl acetate (1 L), 1:9 hexanes:ethyl acetate (1 L), 100% ethyl acetate (1 L), 2% MeOH:CH2Cl2 (1 L), 4% MeOH:CH2Cl2 (1 L)) affords the title compound as a light yellow residue. The residue is dissolved in CH2Cl2 and hexanes are added until cloudy. The solution is placed in the freezer overnight and the title compound as a solid is subsequently filtered and dried (0.020 g).

Provenance & Evidence