Hydrochloric Acid → Ethyl 2-(4-cyano-3-methoxyphenyl)propanoate

HRID 1186979Notes

Reaction equation

HRID 1186979 reaction equation
[H-].[Na+].[CH2:3]([O:5][C:6](=[O:18])[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]#[N:15])=[C:10]([O:16][CH3:17])[CH:9]=1)[CH3:4].[CH3:19]I.Cl>C1COCC1>[C:14]([C:11]1[CH:12]=[CH:13][C:8]([CH:7]([CH3:19])[C:6]([O:5][CH2:3][CH3:4])=[O:18])=[CH:9][C:10]=1[O:16][CH3:17])#[N:15]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 66643843Ethyl 2-(4-cyano-3-methoxyphenyl)acetate

Product 1

HCID 66643920Ethyl 2-(4-cyano-3-methoxyphenyl)propanoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension solution of NaH (0.18 g, 4.6 mmol, 60% dispersion in mineral oil) in THF (50 mL) at ° C. under N2 atm was added a solution of ethyl(4-cyano-3-methoxyphenyl)acetate (1.0 g, 4.6 mmol) in THF (10 mL) drop-wise and the mixture was stirred for 30 min at the same temperature. The mixture was then allowed to warm to ambient temperature. The mixture was then allowed to cool back to 0° C. Methyl iodide (0.28 mL, 4.6 mmol) was added and the reaction mixture was stirred for 1 h. The reaction mixture was acidified with 1 M hydrochloric acid and extracted with EtOAc. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc 15/1) to give ethyl 2-(4-cyano-3-methoxyphenyl)propanoate. 1H NMR (500 MHz, CDCl3) δ 7.53 (d, 1H, J=8 Hz), 6.98 (d, 1H, J=8 Hz), 6.95 (s, 1H), 4.17 (q, 2H, J=3.4 Hz), 3.97 (s, 3H), 3.76 (q, 1H, J=9.1 Hz), 1.53 (d, 3H, J=7.1 Hz), 1.25 (t, 3H, J=7.1 Hz); LCMS: [(M+1)]+=234.28; tR=3.12 min.

Workup

  1. temperatureto cool back to 0° C
  2. stirringthe reaction mixture was stirred for 1 h
  3. extractionextracted with EtOAc
  4. washThe organic layer was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel column chromatography (hexane/EtOAc 15/1)

Sources & evidence

ORD record
ord-27a2193b66b44a2da92e4b27cf175c88
Source dataset
uspto-grants-2014_03
Patent number
US08673920B2

Reaction notes

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