Methyl p-toluenesulfonate → 3-(2,2-Dimethylpropyl)-1-cyclobutene-1-carboxylic acid

HRID 1912065Notes

Reaction equation

HRID 1912065 reaction equation
[CH3:1][C:2]([CH3:20])([CH3:19])[CH2:3][CH:4]1[CH2:7][CH:6]([C:8]([O:10]CC)=[O:9])[CH:5]1N1CCCCC1.C1(C)C=CC(S(OC)(=O)=O)=CC=1>O>[CH3:1][C:2]([CH3:20])([CH3:19])[CH2:3][CH:4]1[CH2:7][C:6]([C:8]([OH:10])=[O:9])=[CH:5]1

Participants

4

Reactant 2

HCID 6645Methyl p-toluenesulfonateHCID 71114785Ethyl 3-(2,2-dimethylpropyl)-2-piperidin-1-ylcyclobutanecarboxylate

Product 1

HCID 866750383-(2,2-Dimethylpropyl)-1-cyclobutene-1-carboxylic acidYield 31.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
105 °C

Procedure

Ethyl 3-(2,2-dimethylpropyl)-2-piperidin-1-ylcyclobutanecarboxylate (1470 g) and methyl p-toluenesulfonate (417 mL) were mixed. After the mixture was stirred at 105° C. for 2 hr, water (2100 mL) was poured into the reaction mixture and the aqueous layer was extracted. The aqueous layer was washed with tert-butyl methyl ether/hexane=1/1 (800 mL) and hexane (600 mL). To the aqueous layer was added potassium hydroxide (663 g) at ice temperature and the mixture was stirred at 100° C. for 2 hr. After the reaction mixture was washed with tert-butyl methyl ether/hexane=1/1 (600 mL×2), concentrated hydrochloric acid (500 mL) and 6 N hydrochloric acid (606 mL) were added to the aqueous layer at ice temperature. The mixture was extracted with ethyl acetate (600 mL×2). The combined organic layer was washed with water (1 L×2) and brine (500 mL), then dried over magnesium sulfate. The magnesium sulfate was filtered off and the filtrate was concentrated in vacuo to give the title compound (278 g) as a crude product.

Workup

  1. extractionthe aqueous layer was extracted
  2. washThe aqueous layer was washed with tert-butyl methyl ether/hexane=1/1 (800 mL) and hexane (600 mL)
  3. additionTo the aqueous layer was added potassium hydroxide (663 g) at ice temperature
  4. stirringthe mixture was stirred at 100° C. for 2 hr
  5. washAfter the reaction mixture was washed with tert-butyl methyl ether/hexane=1/1 (600 mL×2), concentrated hydrochloric acid (500 mL) and 6 N hydrochloric acid (606 mL)
  6. additionwere added to the aqueous layer at ice temperature
  7. extractionThe mixture was extracted with ethyl acetate (600 mL×2)
  8. washThe combined organic layer was washed with water (1 L×2) and brine (500 mL)
  9. dry with materialdried over magnesium sulfate
  10. filtrationThe magnesium sulfate was filtered off
  11. concentrationthe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-82fca84f92c547a8b390e7590c8e8414
Source dataset
uspto-grants-2013_12
Patent number
US08604069B2

Reaction notes

Loading…