Potassium Carbonate → (3-Fluoro-4-formylphenoxy)methyl butyrate

HRID 2370697Notes

Reaction equation

HRID 2370697 reaction equation
[F:1][C:2]1[CH:9]=[C:8]([OH:10])[CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].C([O-])([O-])=O.[K+].[K+].[C:17]([O:22][CH2:23]Cl)(=[O:21])[CH2:18][CH2:19][CH3:20]>CC(C)=O>[C:17]([O:22][CH2:23][O:10][C:8]1[CH:7]=[CH:6][C:3]([CH:4]=[O:5])=[C:2]([F:1])[CH:9]=1)(=[O:21])[CH2:18][CH2:19][CH3:20]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 5872462-Fluoro-4-hydroxybenzaldehydeHCID 2725008Chloromethyl butanoate

Product 1

HCID 58234674(3-Fluoro-4-formylphenoxy)methyl butyrateYield 66.6%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent3×

Procedure

To a 500 mL dry round bottom flask a were added 2-fluoro-4-hydroxybenzaldehyde (5.60 g, 40 mmol), anhydrous K2CO3 (10.6 g, 76.9 mmol) and acetone (200 mL). The mixture was stirred at room temperature for 30 minutes. To another 500 mL dry round bottom flash b were added chloromethyl butyrate (9.33 g, 61.5 mmol), KI (14.2 g, 66.6 mmol) and acetone (150 mL). This mixture was also stirred at room temperature for 30 minutes. After the solid settled down on the glassware bottom, the top yellow acetone solution in flask b was decanted into the stirring solution in the round bottom flask a. The resulting mixture was refluxed for 4 hours. Most acetone was rotary evaporated, and the residual solid was triturated with methyl tert-butyl ether (MTBE) three times (100 mL, 50 mL, 50 mL). The MTBE extract was concentrated, and the residue was purified with a silica gel chromatography (heptane/ethyl acetate, gradient eluting) to give (3-fluoro-4-formylphenoxy)methyl butyrate (6.40 g) as a colorless oil. Yield: 43%. 1H NMR (CDCl3, 300 MHz): δ=10.18 (s, 1H), 7.80 (t, J=8.7 Hz, 1H), 6.93-6.89 (m, 1H), 6.82 (dd, J=12.3, 2.1 Hz, 1H), 5.83 (s, 2H), 2.36 (t, J=7.5 Hz, 2H), 1.64 (sextet, J=7.5 Hz, 2H), 0.92 (t, J=7.5 Hz, 3H). 13C NMR (CDCl3, 75.5 MHz): δ=185.5 (d, J=6.1 Hz), 169.7 (d, J=258.8 Hz), 162.8 (d, J=12.2 Hz), 130.2 (d, J=3.7 Hz), 119.1 (d, J=8.5 Hz), 112.4 (d, J=3.1 Hz), 103.5 (d, J=24.4 Hz), 84.1, 35.7, 18.0, 13.3.

Workup

  1. customTo a 500 mL dry round bottom flask
  2. customTo another 500 mL dry round bottom flash b
  3. stirringThis mixture was also stirred at room temperature for 30 minutes
  4. customwas decanted into the stirring solution in the round bottom flask a
  5. temperatureThe resulting mixture was refluxed for 4 hours
  6. customthe residual solid was triturated with methyl tert-butyl ether (MTBE) three times (100 mL, 50 mL, 50 mL)
  7. extractionThe MTBE extract
  8. concentrationwas concentrated
  9. customthe residue was purified with a silica gel chromatography (heptane/ethyl acetate, gradient eluting)

Sources & evidence

ORD record
ord-dd98d42e76ac414eaabcc9f37af828b6
Source dataset
uspto-grants-2014_04
Patent number
US08710215B2

Reaction notes

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