Potassium Carbonate → 3-Chloro-5-(2-fluoroethoxy)benzaldehyde

HRID 505015Notes

Reaction equation

HRID 505015 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([OH:10])[CH:9]=1)[CH:5]=[O:6].C(=O)([O-])[O-].[K+].[K+].[F:17][CH2:18][CH2:19]CS([O-])(=O)=O>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([O:10][CH2:19][CH2:18][F:17])[CH:9]=1)[CH:5]=[O:6]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 1326223-FluoropropanesulfonateHCID 219046483-Chloro-5-hydroxybenzaldehyde

Product 1

HCID 858230643-Chloro-5-(2-fluoroethoxy)benzaldehydeYield 71.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
100 °C

Procedure

To a solution of 3-chloro-5-hydroxybenzaldehyde (8.2 g, 52.5 mmol; see Preparation A(ii) above) and potassium carbonate (9.4 g, 68.2 mmol) in DMF (10 mL) under nitrogen was added a solution of (2-monofluoroethyl) methanesulfonate (9.7 g, 68.2 mmol; see step (i) above) in DMF (120 mL) dropwise at room temperature. The mixture was heated to 100° C. for 5 h and then stirred overnight at room temperature. The reaction was cooled to 0° C., poured into ice-cold 2N HCl and extracted with EtOAc. The combined organic extracts were washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. The brown oil was chromatographed on silica gel eluting with Hex:EtOAc (4:1) to afford the sub-title compound (7.6 g, 71%) as a yellow oil.

Workup

  1. temperatureThe reaction was cooled to 0° C.
  2. extractionextracted with EtOAc
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe brown oil was chromatographed on silica gel eluting with Hex

Sources & evidence

ORD record
ord-aaa5e9b19f9f4a2293211a79094d275c
Source dataset
uspto-grants-2010_08
Patent number
US07781424B2

Reaction notes

Loading…