Methyl Acrylate → 3-(4-Hydroxymethyl-2-methyl-phenyl)-acrylic Acid Methyl Ester

HRID 860644Notes

Reaction equation

HRID 860644 reaction equation
CO[C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7](Br)=[C:6]([CH3:11])[CH:5]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].[CH3:19][O:20][C:21](=[O:24])[CH:22]=[CH2:23].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)C(C)C)(C)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCCC1>[CH3:19][O:20][C:21](=[O:24])[CH:22]=[CH:23][C:7]1[CH:8]=[CH:9][C:4]([CH2:3][OH:12])=[CH:5][C:6]=1[CH3:11]

Participants

8

Reactant 5

HCID 7294Methyl AcrylateHCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 3294148Methyl 4-bromo-3-methylbenzoateHCID 21226445Aluminium lithium hydride

Product 1

HCID 688380573-(4-Hydroxymethyl-2-methyl-phenyl)-acrylic Acid Methyl Ester

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of methyl-4-bromo-3-methylbenzoate (5.7 g, 24.88 mmol), lithium aluminum hydride (29 mL, 29 mmol, 1 M solution in tetrahydrofuran) and tetrahydrofuran (100 mL) is stirred in ice/water for 1 hr. The reaction is quenched with aqueous hydrochloric acid (50 mL, 1 M). The product is extracted into ethyl acetate (3×100 mL). The combined extracts are dried over anhydrous magnesium sulfate, filtered and concentrated. The crude product is taken up in propionitrile (100 mL). Methylacrylate (10 mL, 121.5 mmol), palladium acetate (1.12 g, 5 mmol), tri-o-tolylphosphine (3.0 g, 10 mmol), and N,N-diisopropyl ethylamine (8.7 mL, 50 mmol) are sequentially added and the resulting reaction mixture is heated to 110 deg C. 3 hr. The mixture is concentrated, and the residue diluted with aqueous hydrochloric acid (100 mL, 1M). The product is extracted with dichloromethane (2×100 mL) and ethyl acetate (100 mL). The combined extracts are dried over anhydrous magnesium sulfate, filtered, concentrated, and purified via silica chromatography eluting with 7:3 hexanes:ethyl acetate to 1:1 hexanes:ethyl acetate to afford the pure product as a yellow oil, 4.7 g, 91%. MS M++1 207. The structure is confirmed by 1H NMR spectroscopy.

Workup

  1. customThe reaction is quenched with aqueous hydrochloric acid (50 mL, 1 M)
  2. extractionThe product is extracted into ethyl acetate (3×100 mL)
  3. dry with materialThe combined extracts are dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customthe resulting reaction mixture
  7. temperatureis heated to 110 deg C
  8. custom3 hr
  9. concentrationThe mixture is concentrated
  10. additionthe residue diluted with aqueous hydrochloric acid (100 mL, 1M)
  11. extractionThe product is extracted with dichloromethane (2×100 mL) and ethyl acetate (100 mL)
  12. dry with materialThe combined extracts are dried over anhydrous magnesium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated
  15. custompurified via silica chromatography
  16. washeluting with 7:3 hexanes

Sources & evidence

ORD record
ord-a4abf82aadfa4a02b27337387ff2e4b8
Source dataset
uspto-grants-2006_12
Patent number
US07153878B2

Reaction notes

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