Lithium Chloride → (4R)-4-methyloctanoic acid

HRID 2216669Notes

Reaction equation

HRID 2216669 reaction equation
[Cl-].[Li+].C([Mg]Br)C.C(Br)[CH2:8][C@H:9]([CH2:11][CH2:12][CH:13]=[C:14](C)C)[CH3:10].CC(=CCC[C@H](C)CCCC)C.C[C:31]([CH3:33])=[O:32].[OH:34]S(O)(=O)=O.O=[Cr](=O)=O>C1COCC1.CC(C)=O.[Cu]Cl>[CH3:8][C@H:9]([CH2:11][CH2:12][CH2:13][CH3:14])[CH2:10][CH2:33][C:31]([OH:34])=[O:32]

Participants

9

Reactant 5

HCID 433294Lithium ChlorideHCID 10900106(S)-(+)-Citronellyl bromideHCID 15291114(6R)-2,6-Dimethyl-2-deceneHCID 131709961Jones' reagentHCID 178418443HCID 178418443, compound

Product 1

HCID 6997333(4R)-4-methyloctanoic acidYield 59.3%

Reagents, catalysts & solvents 3

HCID 62652Cuprous chlorideCatalystHCID 180AcetoneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Lithium chloride (0.39 g, 9.12 mmol) and copper (I) chloride (0.61 g, 4.56 mmol) were combined in 45 ml THF at ambient temperature and stirred 15 minutes, then cooled to 0° C. at which time ethylmagnesium bromide (1 M solution in THF, 45 mL, 45 mmol) was added. (S)-citronellyl bromide (5.0 g, 22.8 mmol) was added dropwise and the solution was allowed to warm slowly to ambient temperature with stirring overnight. The reaction was quenched by cautious addition of sat. NH4Cl (aq), and stirred with Et2O and sat. NH4Cl (aq) for 30 minutes. The phases were separated and the organic phase dried (MgSO4) and concentrated. The crude (R)-2,6-dimethyl-dec-2-ene was used without purification. To a solution of (R)-2,6-dimethyl-dec-2-ene (3.8 g, 22.8 mmol) in 50 mL acetone at 0° C. was added Jones' reagent (2.7 M in H2SO4 (aq), 40 mL, 108 mmol) and the solution was allowed to warm slowly to ambient temperature with stirring overnight. The mixture was partitioned between Et2O and H2O, the phases were separated, and the organic phase washed with brine, dried (MgSO4), and concentrated. The residue was purified by flash chromatography (8:1 hexanes:EtOAc) to afford 2.14 g (59%) of the titled compound as a colorless oil: LRMS: m/z 156.9 (M+); 1H NMR (400 MHz; CDCl3): δ2.33 (m, 2H), 1.66 (m, 1H), 1.43 (m, 2H), 1.23 (m, 5H), 1.10 (m, 1H), 0.86 (m, 6H). Jones' reagent was prepared as a 2.7M solution by combining 26.7 g CrO3, 23 mL H2SO4, and diluting to 100 mL with H2O.

Workup

  1. additionwas added
  2. stirringwith stirring overnight
  3. customThe reaction was quenched by cautious addition of sat. NH4Cl (aq)
  4. stirringstirred with Et2O and sat. NH4Cl (aq) for 30 minutes
  5. customThe phases were separated
  6. dry with materialthe organic phase dried (MgSO4)
  7. concentrationconcentrated
  8. customThe crude (R)-2,6-dimethyl-dec-2-ene was used without purification
  9. temperatureto warm slowly to ambient temperature
  10. stirringwith stirring overnight
  11. customThe mixture was partitioned between Et2O and H2O
  12. customthe phases were separated
  13. washthe organic phase washed with brine
  14. dry with materialdried (MgSO4)
  15. concentrationconcentrated
  16. customThe residue was purified by flash chromatography (8:1 hexanes:EtOAc)

Sources & evidence

ORD record
ord-47d1ad34ac3e466eaf0b32beaddbf796
Source dataset
uspto-grants-2006_09
Patent number
US07112610B2

Reaction notes

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