Dichloromethane → 2'-Cyclohexyl-5'-isopropoxy-4'-methoxyacetophenone

HRID 41944

Reaction equation

HRID 41944 reaction equation
Br[CH:2]1[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.C([Li])(C)(C)C.I[C:14]1[CH:19]=[C:18]([O:20][CH3:21])[C:17]([O:22][CH:23]([CH3:25])[CH3:24])=[CH:16][C:15]=1[C:26](=[O:28])[CH3:27].C(Cl)Cl>CCOCC.C1COCC1.CN(C)C(=O)C.[I-].[Zn+2].[I-].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].[Cu+]>[CH:2]1([C:14]2[CH:19]=[C:18]([O:20][CH3:21])[C:17]([O:22][CH:23]([CH3:25])[CH3:24])=[CH:16][C:15]=2[C:26](=[O:28])[CH3:27])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1

Participants

11

Reactant 4

HCID 6344DichloromethaneHCID 7960Cyclohexyl bromideHCID 667611172'-Iodo-5'-isopropoxy-4'-methoxyacetophenoneHCID 178418306HCID 178418306, compound

Product 1

HCID 680368202'-Cyclohexyl-5'-isopropoxy-4'-methoxyacetophenoneYield 20.2%

Reagents, catalysts & solvents 6

HCID 104815Copper(1+)CatalystHCID 9883512zinc(II)iodideCatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
18 °C

Procedure

A magnetically stirred solution of bromocyclohexane (0.18 mL, 1.46 mmol) in dry Et2O (3.0 mL), under a nitrogen atmosphere, was cooled to −78° C. and treated, dropwise, with tert-butyllithium (1.7 M in pentane, 1.9 mL, 3.23 mmol). After 10 minutes, the mixture was treated, dropwise, with a solution of anhydrous zinc iodide (495 mg, 1.55 mmol) in dry THF (1.7 mL). After 10 minutes at −78° C., the reaction mixture was allowed to warm to 18° C. and then slowly transferred to a mixture of iodide 9 (370 mg, 1.11 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II).CH2Cl2 (18 mg, 0.022 mmol) and copper(I) iodode (8 mg, 0,042 mmol) in N,N-dimethylacetamide (1.0 mL). The resulting mixture was then stirred at 60° C., under a nitrogen atmosphere, for 6 h. The cooled mixture was filtered through a pad of Celite™ and the solids thus retained washed with EtOAC (1×50 mL). The filtrate was then washed with HCl (1×10 mL of a 1.0 M aqueous solution) and brine (1×10 mL), then dried (MgSO4), filtered and concentrated under reduced pressure and the ensuing residue subjected to flash chromatography (1:19→1:9 v/v ethyl acetate/hexane gradient elution) to afford the title compound 52 (65 mg, 20%) as a yellow oil, Rf 0.7 in 1:1 v/v ethyl acetate/hexane.

Workup

  1. additiontreated
  2. additionthe mixture was treated
  3. waitAfter 10 minutes at −78° C.
  4. filtrationThe cooled mixture was filtered through a pad of Celite™
  5. washthe solids thus retained washed with EtOAC (1×50 mL)
  6. washThe filtrate was then washed with HCl (1×10 mL of a 1.0 M aqueous solution) and brine (1×10 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. washthe ensuing residue subjected to flash chromatography (1:19→1:9 v/v ethyl acetate/hexane gradient elution)

Sources & evidence

ORD record
ord-132dd5d15478441f820d511e0facdcaf
Source dataset
uspto-grants-2013_09
Patent number
US08536157B2

Linked notes

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