Dimethylformamide dimethyl acetal → Ethyl 3-(dimethylamino)-2-(4-fluorophenyl)acrylate

HRID 526403Notes

Reaction equation

HRID 526403 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:4][CH:3]=1.CO[CH:16](OC)[N:17]([CH3:19])[CH3:18]>CN(C=O)C.CCOC(C)=O>[CH3:16][N:17]([CH3:19])[CH:18]=[C:8]([C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=1)[C:9]([O:11][CH2:12][CH3:13])=[O:10]

Participants

5

Reactant 2

HCID 78373Dimethylformamide dimethyl acetalHCID 3013910Benzeneacetic acid, 4-fluoro-, ethyl ester

Product 1

HCID 131732875Ethyl 3-(dimethylamino)-2-(4-fluorophenyl)acrylateYield 34.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Combined ethyl 2-(4-fluorophenyl)acetate (500 mg, 2.74 mmol) in 1,1-dimethoxy-N,N-dimethylmethanamine (1.837 mL, 13.72 mmol) and DMF (2 mL) and heated at 100° C. for 5 h. The reaction was then diluted with EtOAc (50 mL), washed with saturated aqueous ammonium chloride (50 mL) and brine, dried over magnesium sulfate and concentrated in vacuo to give a yellow oil. The oil was purified on a 30 g NH silica column (Moritex) eluted with 0 to 60% EtOAc in hexanes to give the title compound (223 mg, 34.2% yield) as a clear, colorless oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.10 (t, J=7.1 Hz, 3H) 2.64 (s, 6H) 3.98 (q, J=7.1 Hz, 2H) 7.06-7.15 (m, 4H) 7.49 (s, 1H).

Workup

  1. washwashed with saturated aqueous ammonium chloride (50 mL) and brine
  2. dry with materialdried over magnesium sulfate
  3. concentrationconcentrated in vacuo
  4. customto give a yellow oil
  5. customThe oil was purified on a 30 g NH silica column (Moritex)
  6. washeluted with 0 to 60% EtOAc in hexanes

Sources & evidence

ORD record
ord-92fe83bf98c94d9b9e4f88e03402210b
Source dataset
uspto-grants-2016_05
Patent number
US09345713B2

Reaction notes

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