Water → (3-Fluorophenyl)carbamic acid benzyl ester

A solution of the 3-fluoro-phenylamine (1015, 18.7 g, 168.3 mmol) in tetrahydrofuran (THF, 150 mL) was treated with potassium carbonate (K2CO3, 46.45 g, 336.6 mmol, 2.0 equiv) and H2O (150 mL) before a solution of benzyl chloroformate (CBZCl, 31.58 g, 185.1 mmol, 26.1 mL, 1.1 equiv) in THF (50 mL) was dropwise added into the reaction mixture at room temperature under N2. The resulting reaction mixture was stirred at room temperature for 2 h. When TLC showed that the reaction was complete, the reaction mixture was treated with H2O (100 mL) and ethyl acetate (EtOAc, 100 mL). Tire two layers were separated, and the aqueous layer was extracted with EtOAc (2×100 mL). The combined organic extracts were washed with H2O (2×100 mL) and saturated NaCl aqueous solution (100 mL), dried over MgSO4, and concentrated in vacuo. The residue was further dried in vacuo to afford the crude, (3-fluoro-phenyl)-carbamic acid benzyl ester (2, 39.2 g, 41.23 g theoretical, 95%) as pale-yellow oil, which was found to be essentially pure and was directly used in the subsequent reactions without further purifications. For 1016: 1H NMR (300 MHz, CDCl3) δ 5.23 (s, 2H, OCH2Ph), 6.75-6.82 (m, 2H), 7.05 (dd, 1H, J=1.4, 8.2 Hz), 7.22-7.45 (m, 6H); C14H12FNO2, LCMS (EI) m/e 246 (M++H).

1. additionwas dropwise added into the reaction mixture at room temperature under N2
2. customThe resulting reaction mixture
3. customTire two layers were separated
4. extractionthe aqueous layer was extracted with EtOAc (2×100 mL)
5. washThe combined organic extracts were washed with H2O (2×100 mL) and saturated NaCl aqueous solution (100 mL)
6. dry with materialdried over MgSO4
7. concentrationconcentrated in vacuo
8. customThe residue was further dried in vacuo

ORD 기록

ord-41869d15cc254eed80544f0ace65ae17

출처 데이터셋

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08399660B2