Ethanol → (E)-3-Cyclohexyl-2-(4-methylsulfanyl-phenyl)-acrylic acid ethyl ester

HRID 2103650Notes

Reaction equation

HRID 2103650 reaction equation
[CH2:1]([O:3][C:4](=[O:14])/[C:5](/Br)=[CH:6]/[CH:7]1[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1)[CH3:2].[CH3:15][S:16][C:17]1[CH:22]=[CH:21][C:20](B(O)O)=[CH:19][CH:18]=1.C(O)C.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C1(P([Pd-4](P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:1]([O:3][C:4](=[O:14])/[C:5](/[C:20]1[CH:21]=[CH:22][C:17]([S:16][CH3:15])=[CH:18][CH:19]=1)=[CH:6]/[CH:7]1[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1)[CH3:2]

Participants

7

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 27339594-(Methylthio)phenylboronic acidHCID 21575668(Z)-Ethyl 2-bromo-3-cyclohexylacrylate

Product 1

HCID 67084522(E)-3-Cyclohexyl-2-(4-methylsulfanyl-phenyl)-acrylic acid ethyl esterYield 87.6%

Reagents, catalysts & solvents 2

HCID 178420553HCID 178420553, compoundCatalystHCID 1140TolueneSolvent

Procedure

Dissolve (Z)-2-bromo-3-cyclohexyl-acrylic acid ethyl ester (76.4 g, 300 mmol) and 4-(methylthio)benzene boronic acid (60.5 g, 360 mmol) in a mixture of 1500 mL toluene, 500 mL ethanol and 2M aqueous sodium carbonate solution (500 mL). Add tetrakis(triphenylphosphino)palladium(0) (10.4 g, 3mol %) and heat the mixture at reflux for 5 h. Cool and remove the ethanol under vacuum. Partition the residue between water (250 mL) and dichloromethane (4×250 mL). Combine the extracts and dry over magnesium sulfate, filter and concentrate. Pass through a silica gel pad with a mix of iso-hexane:dichloromethane:diethyl ether (92:4:4) to give the title compound as a hazy oil (80 g). GC-MS (m/e): 304 (M+).

Workup

  1. temperatureat reflux for 5 h
  2. temperatureCool
  3. customremove the ethanol under vacuum
  4. customPartition the residue between water (250 mL) and dichloromethane (4×250 mL)
  5. dry with materialCombine the extracts and dry over magnesium sulfate
  6. filtrationfilter
  7. concentrationconcentrate
  8. additionPass through a silica gel pad with a mix of iso-hexane:dichloromethane:diethyl ether (92:4:4)

Sources & evidence

ORD record
ord-e277019c2a564ca4b82f393607b7990f
Source dataset
uspto-grants-2009_08
Patent number
US07576108B2

Reaction notes

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