Water → 1-{[1-(4-Iodophenyl)cyclopropyl]methyl}pyrrolidine

Participants

Reaction Steps

Part A. 1-(4-Iodophenyl)cyclopropane carboxylic acid (0.64 g, 2.25 mmol) was stirred in THF (10 mL) at 0° C. under N2. Et3N (0.47 mL, 3.37 mmol) was added, followed by dropwise addition of ClCO2Et (0.28 mL, 2.93 mmol). The reaction mixture was then stirred at 0° C. for 30 min. TLC showed the completion of the reaction. The mixture was filtered through a filter funnel and rinsed with anhydrous THF. The THF filtrate (ca.15 mL) was stirred at 0° C. under N2. NaBH4 (0.41 g, 10.8 mmol) was added, followed by addition of MeOH (3 mL). The resulting mixture was stirred at 0° C. for 30 min. Analytical LC-MS showed completion of the reaction. Sat'd Na2SO4 was then added. The mixture was extracted with EtOAc (2×). The organic layer was washed with H2O (2×) and brine (2×), dried over Na2SO4, filtered, and concentrated to dryness. The resulting alcohol was stirred in anhydrous CH2Cl2 (10 mL) at RT under N2. NaOAc (0.42 g, 5.12 mmol) and molecular sieves (4 Å, 0.75 g) were added, followed by the addition of PCC (0.83 g, 3.84 mmol). The resulting slurry was stirred at RT for 1.5 h. Analytical LC-MS showed completion of the reaction. The mixture was filtered through Celite, and rinsed with CH2Cl2. The filtrate was washed with H2O (2×) and brine (2×), dried over Na2SO4, filtered, and concentrated in vacuo to give almost pure 4-iodophenylcyclopropanecarbaldehyde. This aldehyde and pyrrolidine (0.37 mmol) were stirred in dichloroethane (6 mL) at RT under N2. NaBH(OAc)3 (1.37 mg, mmol) was added, followed by addition of several drops of HOAc. The reaction mixture was stirred at RT for 20 min. Analytical LC-MS showed completion of the reaction. H2O was added. The mixture was extracted with EtOAc; and the organic extracts were washed with H2O (2×) and brine (2×), dried over Na2SO4, filtered, and concentrated to dryness to give almost pure 1-{[1-(4-iodophenyl)cyclopropyl]methyl}pyrrolidine (0.41 g, yield % for 3 steps). LC/MS (ESI+) 328.2 (M+H)+. (10–90% CH3CN/H2O in a 4-min run, tR=1.77 min).

Provenance & Evidence