Triethyl phosphonoacetate → 4-(2-Methoxyphenyl)-3-methyl-but-2-enoic acid ethyl ester

HRID 514031Notes

Reaction equation

HRID 514031 reaction equation
[H-].[Na+].[CH2:3]([O:5][C:6](=[O:16])[CH2:7]P(OCC)(OCC)=O)[CH3:4].[CH3:17][O:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[CH2:25][C:26](=O)[CH3:27]>C1COCC1>[CH2:3]([O:5][C:6](=[O:16])[CH:7]=[C:26]([CH3:27])[CH2:25][C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=1[O:18][CH3:17])[CH3:4]

Participants

5

Reactant 3

HCID 13345Triethyl phosphonoacetateHCID 24758Sodium hydrideHCID 788872-Methoxyphenylacetone

Product 1

HCID 671260684-(2-Methoxyphenyl)-3-methyl-but-2-enoic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

In a 3-neck round bottom flask, fitted with an internal thermometer and addition funnel, a mixture of sodium hydride (60% in mineral oil, 4.14 g) in THF (200 mL), under argon, was cooled to 10° C. (Diethoxyphosphoryl)acetic acid ethyl ester (21 mL) was added dropwise (heat and gas evolution), keeping the internal temperature below room temperature. After addition, the reaction mixture was stirred at room temperature for minutes, and then cooled to 0° C. A solution of 2-methoxyphenyl acetone (5 g) in THF (25 mL) was added dropwise over 5 minutes. The reaction was allowed to warm to room temperature overnight. With active cooling, the reaction was quenched with H2O (200 mL), then AcOH (to pH ˜6) and extracted with EtOAc. The combined organics were washed with NaHCO3, water, and brine, dried over Na2SO4, and concentrated. The crude residue was purified by flash column chromatography to give the desired compound (5.73 g). 1H-NMR: 400 MHz, (CDCl3) δ: 7.24 (app dt, 1H), 7.10 (dd, 1H), 6.92 (d, 1H), 6.88 (d, 1H), 5.58 (s, 1H), 4.13 (q, 2H), 3.82 (s, 3H), 3.46 (s, 2H), 1.26 (t, 3H).

Workup

  1. customIn a 3-neck round bottom flask, fitted with an internal thermometer and addition funnel
  2. additionwas added dropwise
  3. temperature(heat and gas evolution)
  4. customthe internal temperature below room temperature
  5. additionAfter addition
  6. temperaturecooled to 0° C
  7. temperatureto warm to room temperature overnight
  8. customWith active cooling, the reaction was quenched with H2O (200 mL)
  9. extractionAcOH (to pH ˜6) and extracted with EtOAc
  10. washThe combined organics were washed with NaHCO3, water, and brine
  11. dry with materialdried over Na2SO4
  12. concentrationconcentrated
  13. customThe crude residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-71df665003ee4903a8606dd3dc9a2a00
Source dataset
uspto-grants-2015_08
Patent number
US09102614B2

Reaction notes

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