Triethylamine → HCID 68662766, compound

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Reaction Steps

To a solution of [1-(3,5-difluoro-benzyl)-3-(3-ethyl-benzylamino)-2-hydroxy-propyl]-carbamic acid tert-butyl ester (16.1 g, 37 mmol) and triethylamine (6.2 mL, 44 mmol) in 80 mL of anhydrous THF under N2 at 0° C. is added benzylchloroformate (5.8 mL, 41 mmol). The solution is warmed to ambient temperature and stirred for 16 h. The solution is quenched with brine and concentrated to remove most of the THF. The residue is diluted with ethyl acetate and separated. The organic phase is washed with 1 M KH2PO4, saturated NaHCO3 and dried over Na2SO4. The mixture is filtered and concentrated to a white solid which is purified on a BIOTAGE 40M column eluting with 400 mL of heptane followed by 4/1:heptane/EtOAc to obtain [3-tert-butoxycarbonylamino-4-(3,5-difluoro-phenyl)-2-hydroxy-butyl]-(3-ethyl-benzyl)-carbamic acid benzyl ester as a white solid (15 g, 26 mmol, 71%), (MS:M+H: 569.4). This compound (6.0 g, 11 mmol) is dissolved in 10 mL of anhydrous CH2Cl2 at 0° C. and 10 mL of TFA is added. The solution is warmed to ambient temperature and stirred for 3 h. The solution is concentrated, diluted with EtOAc and washed with 1M NaOH. The combined organics are dried (Na2SO4) and the mixture is filtered and concentrated to give desired compound as a white solid (5.0 g, 11 mmol, quant. yield), (MS:M+H, 469.5).

Provenance & Evidence