Anacetrapib-d3 synthesis

Yield:1061715-90-9 58%

Reaction Conditions:

with potassium carbonate in N,N-dimethyl-formamide at 20 - 60;

Steps:

2

Synthesis of (4S,5R)-5-(3,5-bis(trifluoromethyl)phenyl)-3-((4'-fluoro-5'-isopropyl-2'-(d₃-methoxy)-4-(trifluoromethyl)biphenyl-2-yl)methyl)-4-methyl-1,3-oxazolidin-2-one (Compound 101). To a solution of 55 (1.0 g) in DMF (10 mL) was added iodomethane-d₃ (0.3 mL) followed by powdered K₂CO₃ (0.26 g). The mixture was heated at 50-60° C. for 3 hr then stirred at room temperature overnight. The reaction mixture was diluted with MTBE (200 mL) and the solution washed with water (50 mL*3), brine, dried (Na₂SO₄), filtered and the solvent concentrated under reduced pressure. The crude product was purified by chromatography on silica gel to give 620 mg (58%) of Compound 101. MS m/z=641(M+H), 663 (M+Na).

References:

US2008/242711,2008,A1 Location in patent:Page/Page column 15-16