Hydrochloric Acid → 4-(N-tert-butylcarbonyl-3-fluoropropylaminomethyl)phenyl boronic acid

Temperature

-78 °C

To a solution of bromide 115 (3.0 g, 8.7 mmol) in anhydrous THF (30 mL) at −78° C. was added a 2.5 M solution of n-BuLi in hexane (3.64 mL, 9.1 mmol, 1.05 equiv). The resulting reaction mixture was stirred at −78° C. for 1 h before trimethyl borate (B(OMe)3, 1.2 mL, 10.4 mmol, 1.2 equiv) was added dropwise. The resulting reaction mixture was stirred at −78° C. for j 0.5 h before being gradually warmed to room temperature overnight. The reaction mixture was poured into water (60 mL), and the aqueous solution was treated with 1.0 N aqueous HCl to pH 4.0. The aqueous mixture was then extracted with EtOAc (4×30 mL). The combined organic extracts were washed with saturated aqueous NaCl (30 mL), dried over anhydrous Na2SO4, and concentrated in vacuo to obtain the desired 4-(N-tert-butylcarbonyl-3-fluoropropylaminomethyl)phenyl boronic acid 120 (2.5 g). This product was directly used in subsequent reactions without further purification. C15H23BFNO4, HPLC/MS (ESI) m/e 312 (M++H).

1. customThe resulting reaction mixture
2. additionwas added dropwise
3. customThe resulting reaction mixture
4. temperaturebefore being gradually warmed to room temperature overnight
5. extractionThe aqueous mixture was then extracted with EtOAc (4×30 mL)
6. washThe combined organic extracts were washed with saturated aqueous NaCl (30 mL)
7. dry with materialdried over anhydrous Na2SO4
8. concentrationconcentrated in vacuo

ORD record

ord-031aaeae9adf4986aad112a44f5b3132

Source dataset

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08324398B2