1,2-Dichloroethane → [(R)-1-(3'-Chloro-biphenyl-4-ylmethyl)-3-methanesulfonylamino-3-oxo-propyl]-carbamic acid tert-butyl ester

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Reaction Steps

(R)-3-tert-butoxycarbonylamino-4-(3′-chloro-biphenyl-4-yl)-butyric acid ethyl ester (250 mg, 0.598 mmol) is treated with 2M NaOH aqueous solution (1 mL) in THF (1 mL) and EtOH (2 mL). After being stirred for 1 h, the reaction mixture is acidified with 1M HCl and extracted with EtOAc. The organic layer is washed with brine, dried over Na2SO4 and concentrated in vacuo. To a solution of this residue in DMF (2 mL) are added methylsulfonamide (85 mg, 0.897 mmol), EDC (172 mg, 0.897 mmol), HOAt (98 mg, 0.718 mmol), and Et3N (0.125 mL, 0.897 mmol). After being stirred at room temperature overnight, the reaction mixture is diluted with EtOAc, washed with 1M HCl and brine. The organic layer is dried over Na2SO4 and concentrated. The residue is purified by flash column chromatography (silica gel, eluent: DCM/10% MeOH in DCM=100:0 to 0:100) to give [(R)-1-(3′-chloro-biphenyl-4-ylmethyl)-3-methanesulfonylamino-3-oxo-propyl]-carbamic acid tert-butyl ester (244 mg). HPLC retentions time=1.30 minutes (condition B); MS (m+1)=467; 1H NMR (400 Mz, DMSO-d6) δ ppm 1.30 (s, 9 H), 2.41-2.48 (m, 2 H), 2.70-2.78 (m, 2 H), 3.18 (s, 3 H), 3.99-4.11 (m, 1 H), 7.28 (d, 2 H, J=8.34 Hz), 7.38-7.44 (m, 1 H), 7.48 (t, 1 H, J=7.83 Hz), 7.59-7.66 (m, 3 H), 7.69 (s, 1 H).

Provenance & Evidence