N-Methylpropylamine → cis-2-(Methyl-propylcarbamoyl)-cyclopropane carboxylic acid

Participants

Reaction Steps

Add diisopropylethylamine (2.68 mL, 15.4 mmol) and cis-cyclopropane-1,2-dicarboxylic acid (0.50 g, 3.84 mmol) to a slurry of 2-chlorotrityl chloro resin (3.00 g, Nova Bio) in 7:1 dichloromethane:dimethylfomamide (10.0 mL). Stir over night and then filter the slurry. Wash the resin with 17:2:1 dichloromethane:methanol:dimethylformamide (3×20 mL) followed by dichloromethane (3×20 mL). Add the filtered resin to a solution of diisopropylethylamine (1.34 mL, 7.69 mmol), methylpropylamine (0.788 mL, 7.69 mmol), O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HBTU) (2.915 g, 7.69 mmol), and HOBT (1.177 g, 7.69 mmol) in dimethylformamide (10 mL) and shake for 2.5 days. Filter and wash the resin with dimethylformamide (3×20 mL) and dichloromethane (5×20 mL). Add trifluoroacetic acid (1 mL) to a slurry of the washed resin in dichloromethane (20 mL). Shake for 45 minutes and filter. Wash the resin with dichloromethane (2×20 mL) and concentrate this filtrate under reduced pressure. Subject the residue to silica gel chromatography, eluting with dichloromethane containing 10-40% of 5% (2:1 methanol:acetic acid) in dichloromethane to provide the title compound (0.247 g, 34.7%).

Provenance & Evidence