Pyridine → HCID 66961163, compound

Participants

Reaction Steps

The 4-nitrobenzyl (2R)-2-hydroxy-5-(4-methoxyphenyl)pentanoate (5.43 g) described in Reference Example 5 was dissolved in acetonitrile (20 ml), followed by adding thereto trifluoroacetic anhydride (5.1 ml) and then triethylamine (4.2 ml) at −30 to −20° C., and the resulting mixture was allowed to warm to room temperature spontaneously. After 30 minutes, the reaction mixture was poured into a saturated aqueous ammonium chloride solution and extracted with ethyl acetate, and the organic layer was washed with a saturated aqueous sodium hydrogencarbonate solution and a saturated aqueous sodium chloride solution and dried over anhydrous sodium sulfate. After the drying agent was removed by filtration, the solvent was distilled off under reduced pressure and the residue was dissolved in acetonitrile (20 ml). The compound described in Reference Example 6 (ethyl 3-bromo-4-mercaptobenzoate (4.14 g, 15.7 mmol)) and then pyridine (1.28 ml, 15.7 mmol) were added thereto under ice-cooling. After 15 minutes, the resulting mixture was warmed up to room temperature. After 1 hour, the reaction mixture was poured into a saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution and then dried over anhydrous sodium sulfate. The drying agent was removed by filtration and the solvent was distilled off under reduced pressure. The residue was purified by a silica gel column chromatography (hexane/ethyl acetate=4/1) to obtain ethyl 3-bromo-4-[((1S)-4-(4-methoxyphenyl)-1-{[(4-nitrobenzyl)oxy]carbonyl}-butyl)thio]benzoate (6.89 g) having an optical purity of 99% e.e. The optical purity analysis conditions are as follows. [Optical purity analysis conditions: column=OJ-R (Chiralcel, DAICEL Chemical Industries Ltd.); detecting wavelength (UV)=254 nm; flow rate: 1.0 ml/min; mobile phase=acetonitrile/water (68/32)]

Provenance & Evidence