Sodium hydride → (4-Bromo-benzyl)-(3-fluoro-propyl)-carbamic acid tert-butyl ester

To a solution of compound 138 (286 mg, 1.0 mmol) in anhydrous DMF (3.0 mL) was added sodium hydride (NaH, 60% oil dispersion, 48.0 mg, 1.2 mmol, 1.2 equiv) at 0° C. The resulting mixture was stirred at 0° C. for 30 min before 1-bromo-3-fluoropropane 139 (170 mg, 1.2 mmol, 1.2 equiv) was added. The reaction mixture was subsequently warmed to 50–60° C. and stirred for 24 hours. The reaction mixture was then quenched with H2O (10 mL), and the resulting aqueous solution was extracted with EtOAc (2×20 mL). The combined organic extracts were washed with H2O (10 mL) and saturated aqueous NaCl (10 mL), dried over MgSO4 and concentrated in vacuo. The residue was purified by column chromatography (10–15% EtOAc/hexane gradient elution) to afford bromide 136 (158 mg, 46% yield) as a colorless oil.

1. additionwas added
2. temperatureThe reaction mixture was subsequently warmed to 50–60° C.
3. customThe reaction mixture was then quenched with H2O (10 mL)
4. extractionthe resulting aqueous solution was extracted with EtOAc (2×20 mL)
5. washThe combined organic extracts were washed with H2O (10 mL) and saturated aqueous NaCl (10 mL)
6. dry with materialdried over MgSO4
7. concentrationconcentrated in vacuo
8. customThe residue was purified by column chromatography (10–15% EtOAc/hexane gradient elution)

ORD record

ord-54a364ae69a94cb8905445f64cba9a0c

Source dataset

uspto-grants-2006_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07129259B2