Chloroiodomethane → Methyl 3-cyano-4-isopropoxybenzoate

HRID 1785062Notes

Reaction equation

HRID 1785062 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:12]=1[OH:13])[C:6]([O:8][CH3:9])=[O:7])#[N:2].Cl[CH2:15]I.C([Zn][CH2:20][CH3:21])C.[NH4+].[Cl-].[NH4+].[OH-]>ClCCCl.CCOC(C)=O>[C:1]([C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:12]=1[O:13][CH:20]([CH3:21])[CH3:15])[C:6]([O:8][CH3:9])=[O:7])#[N:2]

Participants

8

Reactant 5

HCID 11644ChloroiodomethaneHCID 14923Ammonium HydroxideHCID 25517Ammonium ChlorideHCID 11769089Methyl 3-cyano-4-hydroxybenzoateHCID 178418750HCID 178418750, compound

Product 1

HCID 21956805Methyl 3-cyano-4-isopropoxybenzoateYield 30%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Compound 3 (5.56 g, 24.0 mmol) was added to a solution of chloroiodomethane (5.59 mL, 76.8 mmol) in 1,2-dichloroethane (35 mL) under an atmosphere of nitrogen. The solution was cooled to 0° C. with an ice bath and diethyl zinc (38.4 mL, 1.0 M in hexanes, 38.4 mmol) was added over 10 minutes. The resulting mixture was stirred for 30 minutes and allowed to warm to room temperature. It was again cooled to 0° C. with an ice bath, and saturated aqueous NH4Cl (150 mL) was added, followed by concentrated aqueous NH4OH (25 mL) and EtOAc (200 mL). The layers were separated and the aqueous phase was extracted with additional EtOAc (2×100 mL). The organic phases were combined, dried (Na2SO4) and concentrated to a crude oil which was purified over silica gel (100% hexanes) to yield compound 4 (1.76 g, 7.2 mmol, 30% yield) as a colorless oil which was characterized using 1H NMR.

Workup

  1. temperatureto warm to room temperature
  2. temperatureIt was again cooled to 0° C. with an ice bath
  3. customThe layers were separated
  4. extractionthe aqueous phase was extracted with additional EtOAc (2×100 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated to a crude oil which
  7. customwas purified over silica gel (100% hexanes)

Sources & evidence

ORD record
ord-0e8a3d54af1542a99d90dff7cc6f10d0
Source dataset
uspto-grants-2009_03
Patent number
US07504413B2

Reaction notes

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