تفاعل #1000498

معادلة التفاعل

4-fluorophenyl boronic acid

K3PO4

tricyclohexylphosphine

oxygen

3,5-Diethoxy-4-iodo-benzaldehyde

→

title compound

المردود 83.0%

2,6-Diethoxy-4′-fluoro-biphenyl-4-carbaldehyde

المردود 83.0%

المذيبات

water

toluene

ظروف التفاعل

المعالجة

1. 1
   workup.ADDITIONThe reaction mixture was poured
2. 2
   استخلاصextracted with ethyl acetate (2×200 mL)
3. 3
   غسيلthe combined organic phases washed with a sat. solution of NaCl (2×100 mL) and water (2×100 mL)
4. 4
   تجفيفThe organic phase was dried over Na2SO4
5. 5
   تركيزconcentrated by evaporation under reduced pressure
6. 6
   أخرىthe crude material purified by silica column chromatography
7. 7
   غسيلeluting with a mixture of hexane/ethyl acetate (9:1)
8. 8
   أخرىRecrystallization from hexane/ethyl acetate

الإجراء التجريبي

3,5-Diethoxy-4-iodo-benzaldehyde (14.05 g, 43.89 mmol, 1.0 equiv; prepared as described in WO 01/326 33 A1 (F. Hoffmann-La Roche AG); [CAS RN 338454-05-0]) was dissolved under Ar in toluene (180 mL) and water (20 mL) and treated successively with 4-fluorophenyl boronic acid (12.28 g, 87.78 mmol, 2.0 equiv), K3PO4 (50.12 g, 236.12 mmol, 5.38 equiv), tricyclohexylphosphine (2.80 g, 9.66 mmol, 0.22 equiv) and palladium(II) acetate (1.08 g, 4.83 mmol, 0.11 equiv). The reaction mixture was heated to 100° C. for 18 h under scrupulous exclusion of oxygen, when GC indicated the absence of starting iodo-compound. The reaction mixture was poured on crashed ice/NH4Cl, extracted with ethyl acetate (2×200 mL) and the combined organic phases washed with a sat. solution of NaCl (2×100 mL) and water (2×100 mL). The organic phase was dried over Na2SO4, concentrated by evaporation under reduced pressure and the crude material purified by silica column chromatography eluting with a mixture of hexane/ethyl acetate (9:1). Recrystallization from hexane/ethyl acetate provided 10.44 g (83%) of the title compound as white crystals. MS (EI): 288.2 [M]+.

المصدر