Reaction #340606

Reaction equation

3-(4-chloro-2-fluoro-benzyloxy)-2-hydroxy-benzaldehyde

2-fluoro-ethanol

triphenylphosphine

diisopropyl azodicarboxylate

→

compound

Yield 54.0%

3-(4-Chloro-2-fluoro-benzyloxy)-2-(2-fluoro-ethoxy)-benzaldehyde

Yield 54.0%

Solvents

water

ethyl acetate

tetrahydrofuran

tetrahydrofuran

Conditions

Workup

1. 1
   workup.WAITat 40° C. for 3 days
2. 2
   OtherThe organic layers were collected
3. 3
   Washwashed with brine
4. 4
   Dryingdried over magnesium sulfate
5. 5
   OtherAfter removal of solvent
6. 6
   Otherthe residue was purified by silica gel column chromatography
7. 7
   Washeluting with ethyl acetate in hexanes

Procedure

To a solution of 3-(4-chloro-2-fluoro-benzyloxy)-2-hydroxy-benzaldehyde (93, yyyyl40 mg, 0.5 mmol, prepared by protocol of Example 21, Steps 1 and 2 of Scheme 20, using 4-chloro-2-fluoro-benzyl bromide in place of 4-chloro-benzyl bromide in Step 1) in tetrahydrofuran (8 mL) was added dropwise a mixture of 2-fluoro-ethanol (64 mg, 1.0 mmol), triphenylphosphine (180 mg, 0.7 mmol), and diisopropyl azodicarboxylate (120 mg, 0.6 mol) in tetrahydrofuran (5 ml) at 0° C. The reaction mixture was stirred at 0° C. for 10 minutes and then at 40° C. for 3 days. The reaction mixture was dissolved in water and ethyl acetate. The organic layers were collected, washed with brine, and dried over magnesium sulfate. After removal of solvent, the residue was purified by silica gel column chromatography eluting with ethyl acetate in hexanes to provide the compound as a white solid (94, 88 mg, 54%). MS (ESI) [M+H+]+=327.12.

Source