Ethyl Acetate → (R)-ethyl 2-(4-amino-4-(5-bromo-2-fluorophenyl)-3,3-difluoro-2-methylpentan-2-yloxy)acetate

Participants

Reaction Steps

Dropwise addition of TRIFLUOROMETHANESULFONIC ACID in CH2Cl2 0.25 M (225 ml, 56.3 mmol, Eq: 3) to a solution of (R)-ethyl 2-(4-(5-bromo-2-fluorophenyl)-4-(1,1-dimethylethylsulfonamido)-3,3-difluoro-2-methylpentan-2-yloxy)acetate (RO5545483-000-005) (10 g, 18.8 mmol, Eq: 1.00) in Dichloromethane (188 ml) at 0° C. this reaction mixture was stirred at room temperature for 30 minutes Extracted with sat NaHCO3, CH2Cl2, dried over Na2SO4, filtered off, evaporated, dried in HV to give a brown oil (8.8 g; 114%) The residue was chromatographed, 50 g SiO2 (Flashmaster) with EtOAc 0%-50% in heptane to give (R)-ethyl 2-(4-amino-4-(5-bromo-2-fluorophenyl)-3,3-difluoro-2-methylpentan-2-yloxy)acetate (6.85 g, 16.6 mmol, 88.5% yield) as a light yellow oil.

Provenance & Evidence