Dichloromethane → 5-chloro-2-{[(2,2-difluoroethylidene)amino]-methyl}benzyl-1-[(9-hydroxy-9-H-fluoren-9-yl)carbonyl]-L-prolinamide

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-((9-hydroxy-9H-fluoren-9-yl)carbonyl)-N-(2-aminomethyl-5-chlorobenzyl)-L-prolinamide (65 mg, 0.14 mmol) in anhydrous toluene (1.0 mL) at 0° C. was added difluoroacetaldehyde ethylhemiacetal (20 mg, 0.16 mmol, 1.1 eq). The mixture was heated to 100° C. under nitrogen atmosphere for 40 min and was then treated with MgSO4. Heating was continued for another 2 h. The mixture was then cooled to room temperature and diluted with CH2Cl2. The solution was dried over MgSO4, filtered and concentrated to an orange oil which yielded N-(5-chloro-2-{[(2,2-difluoroethylidene)amino]-methyl}benzyl-1-[(9-hydroxy-9-H-fluoren-9-yl)carbonyl]-L-prolinamide as a foam on prolonged drying under high vacuum. (66 mg, 90%).

Provenance & Evidence