Imidazole → HCID 86186706, compound

HRID 631933Notes

Reaction equation

HRID 631933 reaction equation
[CH2:1]([O:3][C:4](=[O:13])[CH2:5][CH:6]1[CH2:11][CH2:10][CH:9](O)[CH2:8][CH2:7]1)[CH3:2].[I:14]I.N1C=CN=C1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClCCl>[CH2:1]([O:3][C:4](=[O:13])[CH2:5][CH:6]1[CH2:11][CH2:10][CH:9]([I:14])[CH2:8][CH2:7]1)[CH3:2]

Participants

6

Reactant 4

HCID 795ImidazoleHCID 807IodineHCID 11776TriphenylphosphineHCID 14022788HCID 14022788, compound

Product 1

HCID 86186706HCID 86186706, compoundYield 71.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 2-(4-hydroxycyclohexyl)acetic acid ethyl ester (3 g, 16.1 mmol), iodine (6.13 g, 24.2 mmol), imidazole (1.64 g, 24.2 mmol), and triphenylphosphine (6.34 g, 24.2 mmol) was added dichloromethane (100 mL) at room temperature under nitrogen atmosphere. The resulting brown suspension was stirred for 15 h at which time TLC analysis indicated the absence of starting material. Then, the solvent was removed under vacuum and most of the residue was dissolved in ethyl acetate (˜500 mL) and some of the residue was not dissolved which was found to be Ph3PO by 1H NMR. The ethyl acetate solution was washed two times with a solution of water and methanol (3:1) to remove the remaining triphenylphosphineoxide and then washed with brine solution. The organic layer was dried over anhydrous MgSO4, filtered, and concentrated to give the crude residue which was purified using an ISCO (120 g) column chromatography eluting with ethyl acetate in hexanes (0-50%). The desired fractions were combined and the solvent was removed under vacuum to obtain 2-(4-iodocyclohexyl)acetic acid ethyl ester (3.39 g, 71.1% yield) as a viscous light yellow oil. 1H NMR of this product indicated that it contained 30-40% of elimination product (olefin) which was not separable on TLC.

Workup

  1. customThen, the solvent was removed under vacuum and most of the residue
  2. dissolutionwas dissolved in ethyl acetate (˜500 mL)
  3. dissolutionsome of the residue was not dissolved which
  4. washThe ethyl acetate solution was washed two times with a solution of water and methanol (3:1)
  5. customto remove the remaining triphenylphosphineoxide
  6. washwashed with brine solution
  7. dry with materialThe organic layer was dried over anhydrous MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto give the crude residue which
  11. customwas purified
  12. washeluting with ethyl acetate in hexanes (0-50%)
  13. customthe solvent was removed under vacuum

Sources & evidence

ORD record
ord-220762324c824a1e85ffde67965c881d
Source dataset
uspto-grants-2016_04
Patent number
US09321738B2

Reaction notes

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