Boron trifluoride etherate → Methyl 4-((2-hydroxyethoxy)methyl)benzoate

HRID 1479258Notes

Reaction equation

HRID 1479258 reaction equation
[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][OH:11])=[CH:6][CH:5]=1.B(F)(F)F.[CH3:17][CH2:18][O:19]CC.C(OCC)(=O)C>ClCCl>[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][O:11][CH2:17][CH2:18][OH:19])=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 8000Boron trifluoride etherateHCID 8857Ethyl AcetateHCID 81325Methyl 4-(hydroxymethyl)benzoate

Product 1

HCID 23344083Methyl 4-((2-hydroxyethoxy)methyl)benzoateYield 60,329.801%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-5 °C

Procedure

To a flame-dried 2-neck flask was added a solution of methyl-4-(hydroxymethyl)benzoate (2.5 g, 15 mmol) in dichloromethane (30 mL). The reaction was purged with nitrogen and brought to −5° C. A dewar condenser (also flame-dried) containing a dry ice/acetone bath (−78° C.) was affixed to the flask and ethylene oxide-tetradeuterate was added (˜55 drops). Then BF3.Et2O (510 μL, 0.0041 mmol) was added dropwise and the reaction stirred at −5° C. for 35 minutes under nitrogen atmosphere. Monitoring by TLC (100% ethyl acetate) showed complete consumption of the starting material. The reaction was warmed to room temperature and vented to remove any excess ethylene oxide gas. The reaction was then diluted with brine and extracted with dichloromethane (2 times). The combined organics were dried over Na2SO4, filtered, and concentrated under reduced pressure to obtain a crude oil. Purification by flash column chromatography (4:1 pentane:ethyl acetate) provided the product as a clear oil (520 mg, 16% yield). 1H NMR (600 MHz, CDCl3) δ 8.02 (d, 2H, J=8.2 Hz), 7.41 (d, 2H, J=8.1 Hz), 4.62 (s, 2H), 3.92 (s, 3H); 13C NMR (150 MHz, CDCl3167.1, 143.5, 130.8) δ 129.9, 127.5, 72.8, 52.4.

Workup

  1. customThe reaction was purged with nitrogen
  2. custombrought to −5° C
  3. customA dewar condenser (also flame-dried)
  4. additioncontaining a dry ice/acetone bath (−78° C.)
  5. additionwas added (˜55 drops)
  6. customconsumption of the starting material
  7. temperatureThe reaction was warmed to room temperature
  8. customto remove any excess ethylene oxide gas
  9. additionThe reaction was then diluted with brine
  10. extractionextracted with dichloromethane (2 times)
  11. dry with materialThe combined organics were dried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure
  14. customto obtain a crude oil
  15. customPurification by flash column chromatography (4:1 pentane:ethyl acetate)

Sources & evidence

ORD record
ord-af7e708b66b94f2d865385391eaed6f1
Source dataset
uspto-grants-2016_08
Patent number
US09408927B2

Reaction notes

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