4-Methylmorpholine → HCID 131732735, compound

Participants

Reaction Steps

The product from example 191L (0.092 g, 0.116 mmole), (S)-2-(methoxycarbonylamino)-3-methylbutanoic acid (0.020 g, 0.116 mmole) and HOBt (000.018 g, 0.116 mmole) were combined in a 25 mL RB flask and dissolved in DMF (1 mL). The reaction mixture was placed in an ice bath and treated with EDAC (0.022 g, 0.116 mmole) and N-methylmorpholine (0.12 mL, 1.091 mmole. The light yellow reaction mixture was stirred in the ice bath for 1 hr, then stirred at room temperature for 9 hr. The reaction mixture was diluted with EtOAc (100 mL) washed with water (20 mL) and 10% NaCl (20 mL), dried over anhydrous Na2SO4(s), filtered and solvent removed in vacuo leaving an oily residue. The residue was dissolved in 5 mL CH2Cl2 and applied to a 12 g silica gel column. The column was eluted with a gradient of CH2Cl2/MeOH, 99/1 to 95/5 over 22 minutes. The title compound was isolated from the first fraction eluted from the column as a white solid consisting of a mixture of trans-pyrrolidine isomers, 21 mg, 19%. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.71-0.95 (m, 12H) 1.11 (s, 9H) 1.99 (m, 6H) 2.13 (m, 4H) 3.53 (s, 6H) 3.81 (m, 4H) 4.04 (m, 4H) 5.06 (m, 2H) 5.11-5.15 (m, 1H) 5.18-5.26 (m, 1H) 5.32 (m, 1H) 6.25 (m, 2H) 6.86-6.96 (m, 1H) 7.05 (m, 2H) 7.33 (m, 6H) 7.61 (m, 2H) 11.53 (s, 1H) 11.68 (s, 1H) 12.00 (m, 2H); ESI+: 914.5.

Provenance & Evidence