2-(2-phenylmethoxyethoxy)ethyl methanesulfonate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of tert-butyl 3-hydroxy-2,2-dimethylpropanoate (353 mg, 2.03 mmol) and 2-(2-(benzyloxy)ethoxy)ethyl methanesulfonate (47) (500 mg, 1.82 mmol) in DMF (6 mL) at 0° C. was added NaH (60 wt % in oil) (109 mg, 2.73 mmol), and the reaction mixture was allowed to stir at RT for 30 min. The reaction mixture was quenched with sat. NH4Cl (aq.) (1 mL) diluted with water (20 mL) and washed with EtOAc (4×20 mL). The combined organic layers were dried (MgSO4), filtered and concentrated in vacuo. The crude product was purified by silica gel chromatography (12 g, 0-40% Et2O in isohexane) to afford tert-butyl 3-(2-(2-(benzyloxy)ethoxy)ethoxy)-2,2-dimethylpropanoate (48) (619 mg, 96%) as a colourless oil: m/z 375 (M+Na)+ (ES+). 1H NMR (400 MHz, CDCl3) δ: 7.32-7.25 (m, 5H), 4.54 (s, 2H), 3.66-3.56 (m, 8H), 3.41 (s, 2H), 1.40 (s, 8H), 1.10 (s, 6H). The reaction mixture was quenched with sat. NH4Cl (aq.) (1 mL) diluted with water (20 mL) washed with EtOAc (4×20 mL) The combined organic layers were dried (MgSO4) filtered concentrated in vacuo The crude product was purified by silica gel chromatography (12 g, 0-40% Et2O in isohexane)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: MsCl (15.8 mL. 204 mmol) was added to a solution of 2-(2-(benzyloxy)ethoxy)ethanol (46) (25 g, 127 mmol) and Et3N (36 mL, 255 mmol) in DCM (180 mL) at 0° C., the reaction mixture was allowed to warm up to RT and stirred for 16 h. The reaction mixture was diluted with DCM (50 mL) and washed with water (2×50 mL), 1M HCl (aq.) (2×50 mL), the organic layer was dried (MgSO4), filtered and concentrated in vacuo to afford 2-(2-(benzyloxy)ethoxy)ethyl methanesulfonate (47) (35 g, 100%) as an orange oil: m/z 275 (M+H)+ (ES+). 1H NMR (400 MHz, CDCl3) δ: 7.37-7.27 (m, 5H), 4.55 (s, 2H), 4.40-4.37 (m, 2H), 3.78-3.76 (m, 2H), 3.71-3.68 (m, 2H), 3.64-3.62 (m, 2H), 3.02 (s, 3H). washed with water (2×50 mL), 1M HCl (aq.) (2×50 mL) the organic layer was dried (MgSO4) filtered concentrated in vacuo