2,4,5-Trimethylbenzoic acid → HCID 22117219, compound

HRID 1275900Notes

Reaction equation

HRID 1275900 reaction equation
[CH3:1][C:2]1[CH:10]=[C:9]([CH3:11])[C:8]([CH3:12])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].C([N-]C(C)C)(C)C.[Li+].[CH3:21][C:22]1[CH:23]=[C:24]([CH:27]=[CH:28][CH:29]=1)[CH2:25]Br>O1CCCC1.CCCCCCC>[CH3:21][C:22]1[CH:23]=[C:24]([CH2:25][CH2:1][C:2]2[CH:10]=[C:9]([CH3:11])[C:8]([CH3:12])=[CH:7][C:3]=2[C:4]([OH:6])=[O:5])[CH:27]=[CH:28][CH:29]=1

Participants

6

Reactant 3

HCID 107142,4,5-Trimethylbenzoic acidHCID 12099m-Xylyl bromideHCID 2724682Lithium diisopropylamide

Product 1

HCID 22117219HCID 22117219, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8900HeptaneSolvent

Procedure

A solution of the product of step (i)(36.7 g) in tetrahydrofuran (300 ml) was added dropwise to a stirred solution of lithium diisopropylamide (235 ml of a 2.0M solution in heptane) at 10-20° C. The mixture was allowed to warm to room temperature and stirred for 30 minutes then cooled to -20° C. A solution of 3-methylbenzylbromide (36.2 ml) in tetrahydrofuran (100 ml) was added dropwise over 20 minutes. The mixture was allowed to warm to room temperature and stirred for 45 minutes before quenching with 2M HCl and adding ethyl acetate. The organic phase was washed with brine, dried (MgSO4) and concentrated under reduced pressure to 200 ml. Isohexane (200 ml) was added and the crystallised unreacted starting material filtered off. The filtrate was evaporated and the residue partitioned between 2M sodium hydroxide and isohexane. The aqueous phase was acidified to pH 1 with 2M HCl and extracted with dichloromethane. The extract was dried (MgSO4) and evaporated under reduced pressure. Used directly in the next step.

Workup

  1. temperaturethen cooled to -20° C
  2. temperatureto warm to room temperature
  3. stirringstirred for 45 minutes
  4. custombefore quenching with 2M HCl
  5. additionadding ethyl acetate
  6. washThe organic phase was washed with brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated under reduced pressure to 200 ml
  9. additionIsohexane (200 ml) was added
  10. filtrationfiltered off
  11. customThe filtrate was evaporated
  12. customthe residue partitioned between 2M sodium hydroxide and isohexane
  13. extractionextracted with dichloromethane
  14. dry with materialThe extract was dried (MgSO4)
  15. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-b42bb2d8a0854d6891a6a4b1719dfacc
Source dataset
uspto-grants-2000_12
Patent number
US06162808

Reaction notes

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