Hydrochloric Acid → (S)-2-methoxycarbonylamino-3,3-diphenyl-propionic acid

Temperature

0 °C

was prepared as follows: A suspension of L-diphenylalanine (13.87 g, 57.5 mmol) in THF (100 mL), and saturated NaHCO3 (3 mL) being stirred at 0° C. was treated with neat methyl chloroformate (11.81 g, 125 mmol), stirred at 0° C. for 10 minutes and then at room temperature for 14 hours. 1 M HCl was then added and the mixture was extracted with DCM, dried over MgSO4, filtered and concentrated to give the title compound as a white solid, which was used without further purification. MS: m/z=322.1 (MNa+). Part B. The title compound was prepared as follows: To a mixture of N-(1-[4-(aminomethyl)thiophen-2-yl]-2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-N-(3-methylbutyl)benzenesulfonamide (87 mg, 0.227 mmol), N-(methoxycarbonyl)-β-phenyl-L-phenylalanine (75 mg, 0.250 mmol) and Hunig's base (131 μL, 0.751 mmol) in 2.3 mL DMF was added BOP reagent (111 mg, 0.25 mmol). The mixture was stirred at room temperature for 1 hour, and then quenched with saturated NaHCO3. The aqueous layer was extracted 2× with EtOAc, the EtOAc layers were combined and washed 3 times with water, once with brine and dried (MgSO4). The mixture was filtered, concentrated and purified on silica gel (EtOAc/hexanes). MS: m/z=686.2 (MNa+).

1. customwas prepared
2. stirringstirred at 0° C. for 10 minutes
3. extractionthe mixture was extracted with DCM
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated

ORD record

ord-9ce5d62dc84046a6b759a667a53cab12

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09133157B2