Acetone → 5-(5'-Fluoro-2'-methoxyphenyl)pentanal

HRID 1919530Notes

Reaction equation

HRID 1919530 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:13][CH3:14])=[C:6]([CH2:8][CH2:9][CH2:10][CH:11]=O)[CH:7]=1.OS(O)(=O)=O.C[C:21](C)=[O:22]>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:13][CH3:14])=[C:6]([CH2:8][CH2:9][CH2:10][CH2:11][CH:21]=[O:22])[CH:7]=1

Participants

4

Reactant 3

HCID 180AcetoneHCID 1118Sulfuric AcidHCID 252585754-(5-Fluoro-2-methoxyphenyl)butanal

Product 1

HCID 866238615-(5'-Fluoro-2'-methoxyphenyl)pentanalYield 50%

Procedure

To a solution of 9 (0.46 g, 2.0 mmol) in acetone (20 mL) was added H2SO4 (5%, 2 mL) and the reaction was heated to reflux for 1.6 h. After the reaction was cooled to room temperature, most of the solvent was then removed in vacuo. A solution of NaHCO3 (sat. 40 mL) was added and the organics were extracted with EtOAc (3×40 mL) and the combined organic layers were washed with brine (30 mL) and dried over Na2SO4. The crude product obtained by removal of the solvent in vacuo was purified by flash column chromatography on silica (Rf=0.10, EtOAc/Hexane, 10:90, v:v) to give the product (0.20 g, 50%) as oil; 1H NMR (CDCl3, 500 MHz): δ 9.76 (s, 1 H), 6.88-6.82 (m, 2 H), 6.74 (dd, J=4.6, 8.6 Hz, 1 H), 3.79 (s, 3 H), 2.61 (t, J=7.3 Hz, 2 H), 2.45 (m, 2 H), 1.69-1.60 (m, 4 H).

Workup

  1. temperaturethe reaction was heated
  2. temperatureto reflux for 1.6 h
  3. customwas then removed in vacuo
  4. additionA solution of NaHCO3 (sat. 40 mL) was added
  5. extractionthe organics were extracted with EtOAc (3×40 mL)
  6. washthe combined organic layers were washed with brine (30 mL)
  7. dry with materialdried over Na2SO4
  8. customThe crude product obtained by removal of the solvent in vacuo
  9. customwas purified by flash column chromatography on silica (Rf=0.10, EtOAc/Hexane, 10:90, v:v)

Sources & evidence

ORD record
ord-7afb55c94d4248598f1d039f91af419a
Source dataset
uspto-grants-2012_05
Patent number
US08168635B2

Reaction notes

Loading…