Methyl iodide → HCID 18989160, compound

HRID 919005Notes

Reaction equation

HRID 919005 reaction equation
[C:1]([OH:12])(=[O:11])[C:2]1[CH:10]=[CH:9][C:8]2[O:7][CH2:6][O:5][C:4]=2[CH:3]=1.[Li+].[CH3:14]CC[CH2-].IC>O1CCCC1>[CH3:14][C:3]1[C:4]2[O:5][CH2:6][O:7][C:8]=2[CH:9]=[CH:10][C:2]=1[C:1]([OH:12])=[O:11]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 71961,3-Benzodioxole-5-carboxylic acidHCID 61028n-Butyl lithium

Product 1

HCID 18989160HCID 18989160, compoundYield 97.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-75 °C

Procedure

To a round bottom flask equipped with an overhead stirrer and a nitrogen inlet was added piperonylic acid (50.0 g, 301 mmol) and tetrahydrofuran (753 mL). This was cooled to −75° C. in a dry ice-acetone bath. N-Butyllithium (1.6 M in hexanes) (414 mL, 662 mmol) was added dropwise maintaining the temperature of the reaction at or below −65° C. When the addition was complete the cooling bath was removed and the reaction was allowed to warm to −20° C. The reaction was returned to the bath and cooled to at least −60° C. at which time iodomethane (37.5 mL, 602 mmol) was added dropwise. Cooling was removed and the reaction allowed to warm to 10° C. at which time the reaction was placed in an ice bath and stirred at 0° C. for 30 minutes. The reaction was quenched by addition of 1N HCl and the tetrahydrofuran removed by evaporation. The residue was slurried in 1N HCl and filtered. The filtrate was washed with water, and dried at 50-60° C. in vacuo to give a pale yellow solid, 4-methyl-benzo[1.3]dioxole-5-carboxylic acid (52.8 g, 293 mmol) in 97% yield. 1H-NMR (300 MHz, CD3COCD3) δ (ppm): 2.44 (s, 3H), 6.10 (s, 2H), 6.77 (d, 1H), 7.64 (d, 1H). TLC Rf=0.54 (1:1 ethyl acetate/hexane, piperonylic acid=0.41).

Workup

  1. customTo a round bottom flask equipped with an overhead stirrer and a nitrogen inlet
  2. temperaturemaintaining
  3. customthe temperature of the reaction at or below −65° C
  4. additionWhen the addition
  5. customwas removed
  6. temperatureto warm to −20° C
  7. additionwas added dropwise
  8. temperatureCooling
  9. customwas removed
  10. temperatureto warm to 10° C. at which time the reaction
  11. customwas placed in an ice bath
  12. customThe reaction was quenched by addition of 1N HCl
  13. customthe tetrahydrofuran removed by evaporation
  14. filtrationfiltered
  15. washThe filtrate was washed with water
  16. customdried at 50-60° C. in vacuo

Sources & evidence

ORD record
ord-9d5538d82261451fb98694b1dd5c5b7f
Source dataset
uspto-grants-2016_03
Patent number
US09272986B2

Reaction notes

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