Dimethylformamide → 4-(3-Ethyloxetane-3-ylmethoxy)benzoic acid

HRID 2217108Notes

Reaction equation

HRID 2217108 reaction equation
O[C:2]1[CH:12]=[CH:11][CH:10]=[CH:9][C:3]=1[C:4]([O:6]CC)=[O:5].[OH-].[K+].CN(C)C=O.S([O:30][CH2:31][C:32]1([CH2:36][CH3:37])[CH2:35][O:34][CH2:33]1)(C1C=CC(C)=CC=1)(=O)=O>C1(C)C=CC=CC=1.O>[CH2:36]([C:32]1([CH2:31][O:30][C:11]2[CH:12]=[CH:2][C:3]([C:4]([OH:6])=[O:5])=[CH:9][CH:10]=2)[CH2:35][O:34][CH2:33]1)[CH3:37]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 8365Ethyl SalicylateHCID 14797Potassium HydroxideHCID 11425703(3-Ethyloxetan-3-yl)methyl 4-methylbenzenesulfonate

Product 1

HCID 219606314-(3-Ethyloxetane-3-ylmethoxy)benzoic acidYield 84.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

50 g of ethyl hydroxybenzoate and 21 g of potassium hydroxide were added to 400 ml of dimethylformamide, and stirred at 70° C. for 1 hour. This was cooled to 45° C., and 100 g of 3-[(tosyloxy)methyl]-3-ethyloxetane was dropwise added to it. Kept at 45° C., this was stirred for 3 hours. Water and toluene were added to it for liquid-liquid separation. The toluene layer was washed with 3% hydrochloric acid, saturated sodium hydrogencarbonate and water, and then toluene was evaporated away. To the resulting residue, added were 50 g of sodium hydroxide, 500 ml of ethanol and 200 ml of water, and this was refluxed for 2 hours. Ethanol was evaporated away, and the resulting residue was poured into 500 ml of 5% hydrochloric acid, and a crystal was thus formed. The crystal taken out through filtration was recrystallized from a mixed solvent of ethanol and water, and 60 g of 4-(3-ethyloxetan-3-ylmethoxy)benzoic acid (OX5) was obtained. Its melting point was 127.5° C.

Workup

  1. temperatureThis was cooled to 45° C.
  2. stirringKept at 45° C., this was stirred for 3 hours
  3. washThe toluene layer was washed with 3% hydrochloric acid, saturated sodium hydrogencarbonate and water
  4. customtoluene was evaporated away
  5. additionTo the resulting residue, added
  6. temperaturethis was refluxed for 2 hours
  7. customEthanol was evaporated away
  8. additionthe resulting residue was poured into 500 ml of 5% hydrochloric acid
  9. customa crystal was thus formed
  10. filtrationThe crystal taken out through filtration
  11. customwas recrystallized from a mixed solvent of ethanol and water

Sources & evidence

ORD record
ord-86e8f4251a594de8a02ef990e6c0b7a9
Source dataset
uspto-grants-2008_08
Patent number
US07407691B2

Reaction notes

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