Hydrochloric Acid → Methyl 4-(2-fluoroethoxy)benzoate

HRID 1455140Notes

Reaction equation

HRID 1455140 reaction equation
[CH3:1][O:2][C:3](=[O:11])[C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1.[H-].[Na+].Br[CH2:15][CH2:16][F:17].Cl>CN(C=O)C>[F:17][CH2:16][CH2:15][O:10][C:7]1[CH:8]=[CH:9][C:4]([C:3]([O:2][CH3:1])=[O:11])=[CH:5][CH:6]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 7456MethylparabenHCID 129822-Fluoroethyl bromideHCID 24758Sodium hydride

Product 1

HCID 10943448Methyl 4-(2-fluoroethoxy)benzoateYield 85%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Under nitrogen atmosphere to a cold (5° C.) solution of 4-hydroxy-benzoic acid methyl ester (7 g, 46 mmol) in DMF (30 ml) was added NaH (60%; 2.2 g) portion wise over 20 minutes. After the addition was completed, the ice bath was removed and the resulting white suspension was heated up to room temperature and stirred for 3 hours. A prepared solution of 1-Bromo-2-fluoro-ethane (6.42 g, 50 56 mmol) in DMF (20 mL) was added and the new mixture was stirred at 50° C. for 18 hours. After cooling to room temperature the mixture was poured into a mixture of ice and 1 N HCl (1:1) and extracted with ethyl acetate. The organic extracts were washed with brine, dried over MgSO4. Evaporation and purification by flash chromatography (hexane/ethyl acetate 9/1) gave a white solid (7.75. 85% yield); 1H NMR (400 MHZ, CDCl3) δ 3.86 (s, 3H), 4.20 (m, 1H), 4.21 (m, 1H), 4.27 (m, 1H), 4.28 (m, 1H), 6.93 (d, 2H), 7.98 (d, 2H); MS m/e (M+H)+ 198; mp 77° C.

Workup

  1. additionAfter the addition
  2. customthe ice bath was removed
  3. stirringthe new mixture was stirred at 50° C. for 18 hours
  4. temperatureAfter cooling to room temperature the mixture
  5. extractionextracted with ethyl acetate
  6. washThe organic extracts were washed with brine
  7. dry with materialdried over MgSO4
  8. customEvaporation and purification by flash chromatography (hexane/ethyl acetate 9/1)
  9. customgave a white solid (7.75. 85% yield)

Sources & evidence

ORD record
ord-8acb7c455dac46b892aaf99636cd0890
Source dataset
uspto-grants-2009_01
Patent number
US07482349B2

Reaction notes

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