Benzyl Bromide (stabilized with Propylene Oxide)

• Benzyl Bromide (stabilized with Propylene Oxide) (= BnBr) [B0411]
• 4-Bromophenethyl Alcohol [B1918]
• NaH (60%, dispersion in Paraffin Liquid) [S0481]
• THF

4-bromophenethyl alcohol (500 mg, 2.49 mmol) in dry THF (4.0 mL) were added to a suspension of NaH (60%, 219 mg, 5.47 mmol, 2.2 eq.) in dry THF (4.0 mL) at 0 °C. Benzyl bromide (354 µL, 2.98 mmol, 1.2 eq.) was added to the mixture and stirred at room temperature for 1 day. The reaction mixture was quenched with H₂O (10 mL) dropwise at 0 °C and the aqueous layer was extract with ethyl acetate (2 x 10 mL), and washed with brine. Organic layer was dried over sodium sulfate and filtered. The solvent was removed under reduced pressure and the residue was purified by column chromatography (dichloromethane:hexane = 0:100 – 15:85 – 25:75 on silica gel), giving 1 a pale yellow liquid (536.7 mg, 74% yield.).

The reaction mixture was monitored by TLC (ethyl acetate:hexane = 1:10, Rf = 0.55).
Because BnBr has lachrymatory property, this experiment was carried out in the draft chamber.
Since NaH reacts with water to generate hydrogen, which may ignite or explode, water was carefully added dropwise when the reaction was quenched.

Compound 1

¹H NMR (400 MHz, CDCl₃); δ 7.43-7.25 (m, 7H), 7.11 (m, 2 H), 4.51 (s, 2H), 3.66 (t, J = 7.0 Hz, 2H), 2.87 (t, J = 7.0 Hz, 2H).

• Enhancing polo-like kinase 1 selectivity of polo-box domain-binding peptides
• X. Z. Zhao, D. Hymel, T. R. Burke Jr., Bioorg. Med. Chem. 2017, 25, 5041.