Toluene → HCID 123136942, compound

Temperature

-20 °C

To a stirred solution of ethyl 2-((diphenylmethylene)amino)acetate (300 mg, 1.12 mmol) in anhydrous THF (3 mL) at −78° C. was added 0.5 M KHMDS in toluene (2.46 mL, 1.23 mmol). After stirring for 15 min, 2-(4-(bromomethyl)-2-fluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (353 mg, 1.12 mmol) was added. The reaction mixture was stirred at −78° C. for 3 h and warmed to −20° C. To the mixture was added 6 N Hydrochloric acid (0.5 mL) and the mixture was stirred overnight at room temperature. The reaction mixture was diluted with water (5 mL) and 1 N HCl (5 mL) and then extracted with diethyl ether. The aqueous layer was basified with 1N NaOH and then extracted with EtOAc (3×10 mL). The combined organic extract was washed with water, brine and then dried over MgSO4. Filtration and concentration gave 177 mg (46%) of ethyl 2-amino-3-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propanoate which was used in the next step without purification. LCMS-ESI (m/z) calculated for C17H25BFNO4: 337.2. found 338.2 [M+H]+, tR=2.78 min (Method 1).

1. stirringThe reaction mixture was stirred at −78° C. for 3 h
2. stirringthe mixture was stirred overnight at room temperature
3. extractionextracted with diethyl ether
4. extractionextracted with EtOAc (3×10 mL)
5. extractionThe combined organic extract
6. washwas washed with water, brine
7. dry with materialdried over MgSO4
8. filtrationFiltration and concentration

ORD record

ord-b9fad098878f405fac4bf807b9d08c9b

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09260427B2