Triethylamine → HCID 68847889, compound

Participants

Reaction Steps

(±)-2-Ethyl-3-[4-methoxy-3-[[N-[4-(trifluoromethyl)phenyl]carbamoyl]methyl]phenyl]propanoic acid (compound in Example 88: 14.2 g, 34.7 mmol) and dehydrated tetrahydrofuran (100 mL) were mixed under an argon atmosphere, and triethylamine (4.86 ml, 35.0 mmol) and pivaloyl chloride (4.27 mL, 34.7 mmol) were added dropwise under stirring and cooling with ice. Thereafter, the mixture was stirred for 1 hour at room temperature to synthesize mixed acid anhydride. On the other hand, potassium tert-butoxide (4.67 g, 41.6 mmol) and dehydrated tetrahydrofuran (45 mL) were mixed under cooling with ice and argon atmosphere in another vassel, and (S)-4-benzyl-oxazolidine-2-one (7.38 g, 41.6 mmol) dissolved into dehydrated tetrahydrofuran (60 mL) was added dropwise. After completion of the dropwise addition, the mixture was stirred for 30 minutes. Next, a suspension of the mixed acid anhydride synthesized previously was added dropwise while filtering under an atmosphere of argon. After completion of the drop-wise addition, the reaction mixture was concentrated and then poured in water, which was extracted with ethyl acetate. The extracte was washed with 5% hydrochloric acid, saturated aqueous solution of sodium hydrogencarbonate and brine, then dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by means of silica gel column chromatography (eluent: isopropyl ether) to afford 2.65 g (13%) of (4S)-3-[2-ethyl-3-[4-methoxy-3-[[N-[4-(trifluoromethyl)phenyl]carbamoyl]methyl]phenyl]-propanoyl]-4-benzyloxazolidine-2-one with high polarity as a oily product. Also, 3.84 g (20%) of (4S)-3-[2-ethyl-3-[4-methoxy-3-[[N-[4-(trifluoromethyl)phenyl]carbamoyl]-methyl]phenyl]propanoyl]-4-benzyloxazolidine-2-one with low polarity were obtained by purifying by silica gel column chromatography, followed by further recrystallization from a mixed solvent of n-hexane with isopropyl ether, as colorless powder.

Provenance & Evidence