Acetic Acid → Ethyl (2Z)-3-[4-(benzyloxy)-3-methylphenyl]-2-ethoxyacrylate

HRID 353308Notes

Reaction equation

HRID 353308 reaction equation
[CH2:1]([O:8][C:9]1[CH:16]=[CH:15][C:12]([CH:13]=O)=[CH:11][C:10]=1[CH3:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:18]([O:20][CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH3:19].CC(C)([O-])C.[K+].C(O)(=O)C.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1COCC1.C1(C)C=CC=CC=1>[CH2:1]([O:8][C:9]1[CH:16]=[CH:15][C:12](/[CH:13]=[C:21](\[O:20][CH2:18][CH3:19])/[C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:11][C:10]=1[CH3:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 6101p-Toluenesulfonic acidHCID 69955Ethyl ethoxyacetateHCID 202986464-(Benzyloxy)-3-methylbenzaldehydeHCID 23665647Potassium tert-butoxide

Product 1

HCID 68616271Ethyl (2Z)-3-[4-(benzyloxy)-3-methylphenyl]-2-ethoxyacrylateYield 25%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-20 °C

Procedure

4-(Benzyloxy)-3-methylbenzaldehyde (2.36 g; 10.2 mmole) and ethyl ethoxyacetate (1.62 g; 12.3 mmole) were dissolved in dry THF (10 ml) and cooled to −20° C. Potassium tert-butoxide (1.38 g; 12.3 mmole) dissolved in dry tetrahydrofuran (1 ml) was slowly added and the reaction was stirred over night at −20° C. The reaction was quenched with acetic acid (0.80 g; 13.3 mmole). The crude product was isolated, redissolved in toluene and refluxed overnight with p-toluenesulfonic acid (0.18 g; 1.0 mmole) in a Dean-Stark apparatus to separate the water. The solution was cooled, washed with sodium hydrogen carbonate, dried with magnesium sulfate and evaporated. Purification of the crude product with preparative HPLC (Kromasil C8, 10 μm, 50×500 mm) using acetronitrile (50-100%) in ammonium acetate buffer (pH 7) as mobile phase gave 0.86 g (25% yield) of ethyl (2Z)-3-[4-(benzyloxy)-3-methylphenyl]-2-ethoxyacrylate.

Workup

  1. additionwas slowly added
  2. customThe crude product was isolated
  3. customto separate the water
  4. temperatureThe solution was cooled
  5. washwashed with sodium hydrogen carbonate
  6. dry with materialdried with magnesium sulfate
  7. customevaporated
  8. customPurification of the crude product with preparative HPLC (Kromasil C8, 10 μm, 50×500 mm)

Sources & evidence

ORD record
ord-df3f7efd7d2142ceac1d36c76767c65b
Source dataset
uspto-grants-2004_06
Patent number
US06750252B2

Reaction notes

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