Dimethyl Sulfoxide → Methyl 4-(4-(2-tert-butoxy-2-oxoethyl)-2-cyanophenoxy)benzoate

HRID 1927745Notes

Reaction equation

HRID 1927745 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH2:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH:6]=[CH:7][C:8]=1F)#[N:2].[OH:18][C:19]1[CH:28]=[CH:27][C:22]([C:23]([O:25][CH3:26])=[O:24])=[CH:21][CH:20]=1.C([O-])([O-])=O.[K+].[K+].CS(C)=O>O.CCOC(C)=O>[C:14]([O:13][C:11](=[O:12])[CH2:10][C:5]1[CH:6]=[CH:7][C:8]([O:18][C:19]2[CH:20]=[CH:21][C:22]([C:23]([O:25][CH3:26])=[O:24])=[CH:27][CH:28]=2)=[C:3]([C:1]#[N:2])[CH:4]=1)([CH3:17])([CH3:16])[CH3:15]

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 7456MethylparabenHCID 11430Potassium Carbonate2×HCID 45925946Tert-butyl 2-(3-cyano-4-fluorophenyl)acetate

Product 1

HCID 68466372Methyl 4-(4-(2-tert-butoxy-2-oxoethyl)-2-cyanophenoxy)benzoateYield 79%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
90 °C

Procedure

A flask was charged with tert-butyl 2-(3-cyano-4-fluorophenyl)acetate (9.410 g, 40.00 mmol), methyl 4-hydroxybenzoate (7.303 g, 48.00 mmol), K2CO3 (6.634 g, 48.00 mmol), and DMSO (160 mL). The mixture was heated to 90° C. under a nitrogen atmosphere for 17 hours. The mixture was cooled to ambient temperature and poured into a mixture of EtOAc (250 mL) and 10% K2CO3 solution (250 mL). The resulting insoluble residue was dissolved in water and added to the EtOAc-aqueous mixture. The mixture was stirred for 1 hour and layers were separated. The aqueous layer was extracted with EtOAc, and the combined extracts were washed with saturated K2CO3, water, and brine, dried over MgSO4, filtered through a Celite pad, and concentrated under reduced pressure to give 14.7 g of crude product as an oil. The crude material was purified by silica gel chromatography to provide methyl 4-(4-(2-tert-butoxy-2-oxoethyl)-2-cyanophenoxy)benzoate (11.6 g, 79%) as a white solid.

Workup

  1. temperatureThe mixture was cooled to ambient temperature
  2. customlayers were separated
  3. extractionThe aqueous layer was extracted with EtOAc
  4. washthe combined extracts were washed with saturated K2CO3, water, and brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered through a Celite pad
  7. concentrationconcentrated under reduced pressure
  8. customto give 14.7 g of crude product as an oil
  9. customThe crude material was purified by silica gel chromatography

Sources & evidence

ORD record
ord-cc887463d57f465b9ff726ddcaa0d9ac
Source dataset
uspto-grants-2012_05
Patent number
US08183289B2

Reaction notes

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