Sodium Bicarbonate → Ethyl 4-[2-(hydroxyamino)-2-oxoethyl]-2-[3-(4-methoxyphenyl)propyl]-3-oxo-3,4-dihydro-2H-1,4-benzothiazine-6-carboxylate

Participants

Reaction Conditions

Reaction Steps

In THF (40 ml) was dissolved {(2S)-6-(ethoxycarbonyl)-2-[3-(4-methoxyphenyl)propyl]-3-oxo-2,3-dihydro-4H-1,4-benzothiazin-4-yl}acetic acid (the compound of Reference Example 11) (2.06 g), and isobutyl chloroformate (0.72 ml) and N-methylmorpholine (0.51 ml) were added thereto at −20° C. and stirred at −10 to −20° C. for 30 minutes. After O-(trimethylsilyl)hydroxylamine (0.87 ml) was added thereto, the resulting mixture was warmed up to room temperature and stirred for 1 hour. The reaction mixture was poured into a saturated aqueous sodium hydrogencabonate solution and extracted with ethyl acetate, and the organic layer was washed with a saturated aqueous ammonium chloride solution and 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 recrystallized from a mixed solvent of ethyl acetate and diisopropyl ether to obtain (−)-ethyl 4-[2-(hydroxyamino)-2-oxoethyl]-2-[3-(4-methoxyphenyl)propyl]-3-oxo-3,4-dihydro-2H-1,4-benzothiazine-6-carboxylate (1.69 g, 99.9% e.e.). The optical purity analysis conditions are as follows. [Column: AD-H(CHIRALCEL, DAICEL Chemical Industries Ltd.); detecting wavelength (UV): 254 nm; flow rate: 1.0 ml/min; mobile phase: n-hexane/isopropyl alcohol/TFA=80/20/0.1]

Provenance & Evidence