Benzyl Chloromethyl Ether

• Benzyloxymethyl Chloride (= BOM-Cl) [B1207]
• Z-Ser-OMe [C1403]
• N,N-Diisopropylethylamine (= DIEA) [D1599]
• Dichloromethane

DIEA (0.2 mL, 1.18 mmol, 1.5 eq.) and BOM-Cl (135 µL, 0.95 mmol, 1.2 eq.) were added to a solution of Z-Ser-OMe (200 mg, 0.79 mmol) in dichloromethane (3.9 mL) at room temperature. The reaction mixture was stirred for overnight. Additional DIEA (0.4 mL, 2.3 mmol, 3.0 eq.) and BOM-Cl (270 µL, 1.90 mmol, 2.4 eq.) were added and stirred for 8 h. The reaction mixture was quenched with sat. NaHCO₃ aq. (5 mL) and extract with dichloromethane (3 x 5 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 (ethyl acetate:hexane = 1:99 - 10:90 - 33:67 on silica gel), giving 1 as a colorless liquid (194 mg, 66% yield).

The reaction mixture was monitored by TLC (ethyl acetate:hexane = 1:1, Rf = 0.68).
About 19% of Z-Ser-OMe was recovered.

compound 1

¹H NMR (270 MHz, CDCl₃); δ 7.36-7.28 (m, 10H), 5.67 (brd, J = 8.4 Hz, 1H), 5.13 (s, 2H), 4.72 (s, 2H), 4.57 (m, 1H), 4.53 (s, 2 H), 4.12 (m, 1H), 3.81 (dd, J = 3.0, 10.0 Hz, 1H), 3.76 (s, 3H).

• Effective and mild method for preparation of optically active α-amino aldehydes via TEMPO oxidation
• J. Jurczak, D. Gryko, E. Kobrzycka, H. Gruza, P. Prokopowicz, Tetrahedron 1998, 54, 6051.