2-Iodobutane → HCID 53704720, compound

HRID 1601647Notes

Reaction equation

HRID 1601647 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([SH:8])=[CH:4][CH:3]=1.C[O-].[Na+].[CH3:12][C:13]([CH3:22])([CH3:21])[C:14]#[C:15][C:16]([O:18]CC)=[O:17].I[CH:24]([CH2:26][CH3:27])[CH3:25].[OH-].[K+]>CO.O>[CH3:25][CH:24]([O:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][C:14]([C:13]([CH3:12])([CH3:21])[CH3:22])=[CH:15][C:16]([OH:18])=[O:17])=[CH:4][CH:3]=1)[CH2:26][CH3:27]

Participants

8

Reactant 5

HCID 105592-Iodobutane3×HCID 14797Potassium HydroxideHCID 2401474-MercaptophenolHCID 639960HCID 639960, compoundHCID 10942334Sodium Methoxide3×

Product 1

HCID 53704720HCID 53704720, compoundYield 68%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

A solution of p-hydroxythiophenol (64.4 g of 98% pure material, 0.5 mole) in methanol (50 mL) was added dropwise to sodium methoxide (252 mL of a 25% solution in methanol) in a 1 liter, three-neck, round-bottomed flask which had been cooled to 0° C. The resultant reaction mixture was warmed to room temperature, stirred for 1 hour, then again cooled using an ice bath. Ethyl 4,4-dimethylpent-2-ynoate (78 g of 99% pure material, 0.5 mole, prepared in Part A above) was then added dropwise to the reaction mixture over a period of 1.5 hours. The ice bath was then removed, and the reaction mixture was allowed to warm to room temperature and stirred for 2 hours. It was then again cooled, using an ice bath, and 2-iodobutane (110.5 g, 0.6 mole) was added. After the addition had been completed, the resultant mixture was heated to reflux for 3 hours, allowed to stand overnight, and again cooled with an ice bath. Further quantities of sodium methoxide (57 mL of a 25% solution) and 2-iodobutane (46 mL, 0.4 mole) were added, and the reaction mixture was heated at reflux for 3 hours. The process of cooling, addition of sodium methoxide and 2-iodobutane, and heating to reflux was then repeated. The reaction mixture was then cooled to room temperature, potassium hydroxide (100 mL of a 45% aqueous solution) and water (100 mL) were added, and the reaction mixture was heated to 50-60° C. for 2 hours. The volume of the solution was then reduced by about 50%, using a rotary evaporator, after which the concentrated solution was diluted with water (500 mL) and extracted with hexanes. The aqueous layer was cooled and acidified with cold concentrated hydrochloric acid. The material which precipitated (consisting of a mixture of 3-[4-[but-2-oxy]phenylthio]-4,4-dimethylpent-2-enoic acid and dealkylated material, 4,4-dimethyl-3-[4-hydroxyphenylthio]pent-2-enoic acid) was separated and washed with water. The dealkylated material was separated by dissolving the residue in dichloromethane and filtering (the yield of this undesired material was 29.5 g, 23%). The filtrate was concentrated under reduced pressure to give the desired acid (106 g, 68% yield).

Workup

  1. customThe resultant reaction mixture
  2. temperaturewas warmed to room temperature
  3. temperatureagain cooled
  4. additionwas then added dropwise to the reaction mixture over a period of 1.5 hours
  5. customThe ice bath was then removed
  6. temperatureto warm to room temperature
  7. stirringstirred for 2 hours
  8. temperatureIt was then again cooled
  9. additionAfter the addition
  10. temperatureto reflux for 3 hours
  11. waitto stand overnight
  12. temperatureagain cooled with an ice bath
  13. temperaturethe reaction mixture was heated
  14. temperatureat reflux for 3 hours
  15. temperatureThe process of cooling
  16. temperatureheating
  17. temperatureto reflux
  18. temperatureThe reaction mixture was then cooled to room temperature
  19. temperaturethe reaction mixture was heated to 50-60° C. for 2 hours
  20. customa rotary evaporator
  21. additionafter which the concentrated solution was diluted with water (500 mL)
  22. extractionextracted with hexanes
  23. temperatureThe aqueous layer was cooled
  24. customThe material which precipitated (
  25. additionconsisting of a mixture of 3-[4-[but-2-oxy]phenylthio]-4,4-dimethylpent-2-enoic acid
  26. customwas separated
  27. washwashed with water
  28. customThe dealkylated material was separated
  29. dissolutionby dissolving the residue in dichloromethane
  30. filtrationfiltering (the yield of this undesired material
  31. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-592cf6bbdf034ec19ac17ff200dee315
Source dataset
uspto-grants-1999_11
Patent number
US05977351

Reaction notes

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