Ethanol → (5S)-{4'-[5-(acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2'-fluoro-biphenyl-4-ylmethyl}-(3-fluoro-propyl)-carbamic acid tert-butyl ester

A solution of boronic ester 123 (1.40 g, 3.7 mmol, 1.3 equiv) and (4-bromo-benzyl)-(3-fluoro-propyl)-carbamic acid tert-butyl ester 115 (1.0 g, 2.89 mmol, prepared as described in Example 1, above) in a mixture of 1,4-dioxane (21 mL), EtOH (7.0 mL) and H2O (7.0 mL) was treated with solid potassium carbonate (1.2 g, 8.7 mmol, 3.0 equiv) at room temperature. The resulting reaction mixture was degassed three times under a steady stream of argon before being treated with Pd(dppf)2Cl2 (118 mg, 0.144 mmol, 0.05 equiv) at room temperature. The reaction mixture was degassed three times under a steady stream of argon before being warmed to reflux for 2 h. When TLC and HPLC/MS showed the reaction was complete, the reaction mixture was cooled to room temperature before being treated with water (60 mL). The aqueous solution was then extracted with CH2Cl2 (3×20 mL), and the combined organic extracts were washed with water (2×20 mL) and saturated aqueous NaCl (20 mL), dried over MgSO4, and concentrated in vacuo. The residue was purified by flash column chromatography (0-5% MeOH—CH2Cl2 gradient elution) to afford the desired (5S)-{4′-[5-(acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-biphenyl-4-ylmethyl}-(3-fluoro-propyl)-carbamic acid tert-butyl ester 121 (1.36 g, 91% yield) as a colorless oil, which solidified upon standing at room temperature in vacuo.

1. customThe resulting reaction mixture
2. customwas degassed three times under a steady stream of argon
3. customThe reaction mixture was degassed three times under a steady stream of argon
4. temperaturebefore being warmed
5. temperatureto reflux for 2 h
6. additionbefore being treated with water (60 mL)
7. extractionThe aqueous solution was then extracted with CH2Cl2 (3×20 mL)
8. washthe combined organic extracts were washed with water (2×20 mL) and saturated aqueous NaCl (20 mL)
9. dry with materialdried over MgSO4
10. concentrationconcentrated in vacuo
11. customThe residue was purified by flash column chromatography (0-5% MeOH—CH2Cl2 gradient elution)

ORDレコード

ord-4a21a7251c4a430991661f7b650cfac6

出典データセット

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08895741B2