Triethyl phosphite → (E)-Ethyl 3-(dimethylamino)-5-(4-(methoxymethoxy)-3,5-dimethylstyryl)benzoate

HRID 2368875Notes

Reaction equation

HRID 2368875 reaction equation
Cl[CH2:2][C:3]1[CH:4]=[C:5]([CH:11]=[C:12]([N:14]([CH3:16])[CH3:15])[CH:13]=1)[C:6]([O:8][CH2:9][CH3:10])=[O:7].C(OP(OCC)OCC)C.C[O-].[Na+].[CH3:30][O:31][CH2:32][O:33][C:34]1[C:41]([CH3:42])=[CH:40][C:37]([CH:38]=O)=[CH:36][C:35]=1[CH3:43]>CCOC(C)=O.CCO.CN(C=O)C>[CH3:15][N:14]([CH3:16])[C:12]1[CH:11]=[C:5]([CH:4]=[C:3](/[CH:2]=[CH:38]/[C:37]2[CH:40]=[C:41]([CH3:42])[C:34]([O:33][CH2:32][O:31][CH3:30])=[C:35]([CH3:43])[CH:36]=2)[CH:13]=1)[C:6]([O:8][CH2:9][CH3:10])=[O:7]

Participants

8

Reactant 4

HCID 31215Triethyl phosphiteHCID 10942334Sodium MethoxideHCID 199197474-(Methoxymethoxy)-3,5-dimethylbenzaldehydeHCID 68335175Ethyl 3-(chloromethyl)-5-(dimethylamino)benzoate

Product 1

HCID 68335176(E)-Ethyl 3-(dimethylamino)-5-(4-(methoxymethoxy)-3,5-dimethylstyryl)benzoateYield 67.1%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Compound 3 (1.224 g, 4.277 mmol) and triethylphosphite (1.512 mL, 8.555 mmol) were heated to 150° C. for 3 hours. The reaction mixture was cooled to 0° C. and then 6 mL of DMF and 6 mL of EtOH were added. NaOMe (486 mg, 8.554 mmol) and 4-(methoxymethoxy)-3,5-dimethylbenzaldehyde (0.831 g, 4.277 mmol) were added to the solution. After 18 hours, the mixture was diluted with EtOAc and the solution was washed with brine. After drying on Na2SO4, the organic layer was filtered and concentrated under reduced pressure. The residue was subjected to chromatography over silica gel (Hexanes/EtOAc=9/1) to give Compound 4 (1.10 g, 67%). 1H-NMR (500 MHz, CDCl3) δ 7.56 (s, 1H), 7.30 (m, 1H), 7.20 (s, 2H), 7.06 (d, J=16.3 Hz, 1H), 6.99 (d, J=16.3 Hz, 1H), 6.97 (s, 1H), 4.96 (s, 2H), 4.39 (q, J=7.1 Hz, 2H), 3.62 (s, 3H), 3.03 (s, 6H), 2.32 (s, 6H), 1.42 (t, J=7.1 Hz, 3H); 13C-NMR (125 MHz, CDCl3) δ 167.23, 154.65, 150.72, 138.36, 133.12, 131.48, 131.24, 128.70, 127.78, 127.07, 115.70, 114.53, 112.47, 99.11, 60.92, 57.39, 40.65, 16.99, 14.40; ESI-MS: m/z (MH+): 384.2169 (calc'd), 384.2173 (found).

Workup

  1. washthe solution was washed with brine
  2. customAfter drying on Na2SO4
  3. filtrationthe organic layer was filtered
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-ef0868bad66a4a21addde9927a991964
Source dataset
uspto-grants-2014_04
Patent number
US08703815B2

Reaction notes

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