Diisopropylethylamine → (2S,3S,4S)-2-(3-Bromo-2-fluoro-phenylcarbamoyl)-4-fluoro-3-methoxy-pyrrolidine-1-carboxylic acid tert-butyl ester

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Reaction Steps

To a solution of (2S,3S,4S)-4-fluoro-3-methoxy-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester and (2R,3R,4R)-3-fluoro-4-methoxy-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (prepared as described in Scheme B25, 100 mg, 0.380 mmol) in CH2Cl2 (2.4 mL) at 0° C. under nitrogen atmosphere was added 1-chloro-N,N,2-trimethylprop-1-en-1-amine (50.8 mg, 0.38 mmol) and the mixture was stirred at this temperature for 2 h. 3-Bromo-2-fluoroaniline (144 mg, 0.76 mmol) was then added, followed by DIPEA (0.265 mL, 1.52 mmol) and the mixture was stirred at RT for 1 h. The reaction mixture was concentrated and the crude residue was purified by preparative HPLC (Waters Sunfire C18-ODB, 5 μm, 30×100 mm, eluent: 0-0.5 min 5% CH3CN in H2O Flow: 5 mL/min, 0.5-18.5 min 5 to 100% CH3CN/H2O Flow: 40 mL/min, 18.5-20 min 100% CH3CN, CH3CN and H2O both containing 0.1% TFA). The purified HPLC fractions were neutralized by addition of a saturated aqueous solution of Na2CO3, the layer were separated and the aqueous layer was extracted with CH2Cl2 (×2). The combined organic extracts were dried (Na2SO4), filtered and concentrated. White solid. Rf, TLC (c-hexane/EtOAc 1:1)=0.75; MS (UPLC): 435.1/437.1 [M+H]+, 433.1/435.1 [M−H]−; tR (HPLC conditions f): 2.06 min.

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