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Hydrochloric Acid → 3-[4-(3-Benzyloxy-5-methyl-phenoxy)-2-methyl-phenyl]-acrylic acid ethyl ester

HRID 1822283
Notes
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Reaction equation

HRID 1822283 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([OH:16])[CH:12]=[C:13]([CH3:15])[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:17]([O:19][C:20](=[O:31])[CH:21]=[CH:22][C:23]1[CH:28]=[CH:27][C:26](F)=[CH:25][C:24]=1[CH3:30])[CH3:18].C(=O)([O-])[O-].[K+].[K+].Cl>CS(C)=O.CCOCC>[CH2:17]([O:19][C:20](=[O:31])[CH:21]=[CH:22][C:23]1[CH:28]=[CH:27][C:26]([O:16][C:11]2[CH:12]=[C:13]([CH3:15])[CH:14]=[C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH:10]=2)=[CH:25][C:24]=1[CH3:30])[CH3:18]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 109983793-(Benzyloxy)-5-methylphenolHCID 537177243-(4-Fluoro-2-methyl-phenyl)-acrylic acid ethyl ester

Product 1

HCID 690796773-[4-(3-Benzyloxy-5-methyl-phenoxy)-2-methyl-phenyl]-acrylic acid ethyl esterYield 58.6%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 3-benzyloxy-5-methyl-phenol (3.24 g, 15.1 mmol), 3-(4-fluoro-2-methyl-phenyl)-acrylic acid ethyl ester (3.15 g, 15.1 mmol) and 325 mesh potassium carbonate (2.51 g, 18.2 mmol) in dry DMSO (40 mL) is heated to 130° C. and stirred for 20 hours under N2. The reaction is cooled and acidified with 1 N HCl (30 mL). The mixture is then diluted with Et2O and extracted with water. The organic layer is dried (Na2SO4), and the solvent is removed in vacuo to afford crude product that is absorbed on silica gel and purified by flash chromatography using 9/1 hexanes/ethyl acetate to afford 3.56 g (58%) of the title compound. Rf=0.39 (4/1 hexanes/EtOAc). 1H NMR (400 MHz, CDCl3); MS (ES+) m/z mass calculated for C26H26O4 402, found 403 (M+1, 100%).

Workup

  1. temperatureThe reaction is cooled
  2. extractionextracted with water
  3. dry with materialThe organic layer is dried (Na2SO4)
  4. customthe solvent is removed in vacuo
  5. customto afford crude product that
  6. customis absorbed on silica gel
  7. custompurified by flash chromatography

Sources & evidence

ORD record
ord-f68ddca77c1d4435a48459c8f2bbe4d8
Source dataset
uspto-grants-2009_10
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07608639B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes