1-(chloromethoxy)-2-methoxyethane

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To an ice cooled solution of (2S)-6-benzyloxy-1-(4-fluorophenoxy)-hex-4-yn-2-ol (2 g, 6.4 mmol) in dry CH2Cl2 (8 ml) was added N-ethyldiisopropylamine (1.7 ml 9.5 mmol) and stirred for 10 minutes MEM-chloride (1.1 ml, 9.5 mmol) was added to the solution at 0° C. and stirred for 3 h at room temperature. The solvent was concentrated and the residue purified on a silica gel column using EtOAc-light petroleum (1:4) as eluent to yield (2S)-6-benzyloxy-1-(4-fluorophenoxy)-2-(methoxyethoxymethyloxy)-hex-4-yne (2.2 g, 85%) as a yellow colour liquid. TLC:ethyl acetate-light petroleum (1:3), Rf=0.5 1H NMR (CDCl3, 200 MHz): δ 2.65-2.75 (m, 2H), 3.39 (s, 3H), 3.55 (t, J=4.8 Hz, 2H 3.78 (t, J=4.8 Hz, 2H), 4.11 (s, 2H), 4.16 (m, 3H), 4.56 (s, 2H), 4.89 (s, 2H), 6.8-7.02 (m, 4H), 7.3-7.35 (m, 5H). was added to the solution at 0° C. The solvent was concentrated the residue purified on a silica gel column

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

Procedure: To a mixture of 4,5,6-trichloro-1H-benzoimidazole (0.098 g, 0.446 mmol) and THF (2.5 mL) was added DIPEA (0.155 mL, 0.892 mmol), followed by 1-chloromethoxy-2-methoxy-ethane (0.057 ml, 0.49 mmol) at 23° C. After stirring for 18 h, EtOAc was added. The organic layer was washed with saturated aqueous NaHCO3. The aqueous layer was further extracted with EtOAc. The organic layer was dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified (FCC) to yield the titled compound as a mixture of regioisomers (0.084 g, 61%). MS (ESI/CI): mass calcd. for C11H11Cl3N2O2, 308.0; m/z found, 309.0 [M+H]+. 1H NMR (400 MHz, DMSO-d6): 8.59 (s, 1H), 8.58 (s, 1H), 8.09 (s, 1H), 8.04 (d, J=8.5 Hz, 1H), 5.84 (s, 2H), 5.71 (s, 2H), 3.59-3.57 (m, 2H), 3.56-3.53 (m, 2H), 3.42-3.38 (m, 4H), 3.18 (s, 3H), 3.17 (s, 3H). The organic layer was washed with saturated aqueous NaHCO3 The aqueous layer was further extracted with EtOAc The organic layer was dried over MgSO4 filtered concentrated under reduced pressure The residue was purified (FCC)