Ethyl Acetate → HCID 86704075, compound

Participants

Reaction Steps

4-((2R,3S,4R,5S)-3-(3-Chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoic acid (prepared as described in US20100152190A1, 119.9 mg, 194 μmol) was suspended in methylene chloride (5 mL), then N,N-diisopropylethylamine (156 mg, 210 μL, 1.21 mmol) was added, followed by (2-(7-aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate) (HATU, 120 mg, 316 μmol). After stirring at room temperature under argon for a few minutes, DL-alaminol (24.1 mg, 25 μL, 321 μmol) was added. The reaction progress was monitored by LC-MS. After its completion (˜2 h), the reaction mixture was taken in ethyl acetate (75 mL) and water (15 mL). The layers were separated, and the organic layers were washed with saturated solution of sodium bicarbonate (10 mL), water (15 mL), brine (15 mL), and dried over anhydrous sodium sulfate. The solids were filtered off, and the crude residue was purified by flash chromatography (8 g of silica gel, eluting with 0.5-5.0% ethanol in methylene chloride) to give rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-N-(4-(1-hydroxypropan-2-ylcarbamoyl)-2-methoxyphenyl)-5-neopentylpyrrolidine-2-carboxamide (118.9 mg, 177 μmol, 90.8% yield) as white solids. MS (ES+) m/z calcd. for C34H37Cl2F2N4O4: [(M+H)+]: 673. found: 673.

Provenance & Evidence