Triethyl phosphonoacetate → 3-{4-[Dimethylamino-(3-fluorophenyl)-methyl]-cyclohexyl}-acrylic acid ethyl ester

HRID 557522Notes

Reaction equation

HRID 557522 reaction equation
CC([O-])(C)C.[K+].[CH3:7][CH2:8][O:9][C:10]([CH2:12]P(OCC)(OCC)=O)=[O:11].[CH3:21][N:22]([CH:24]([C:33]1[CH:38]=[CH:37][CH:36]=[C:35]([F:39])[CH:34]=1)[CH:25]1[CH2:30][CH2:29][CH:28]([CH:31]=O)[CH2:27][CH2:26]1)[CH3:23]>CN(C=O)C>[CH2:8]([O:9][C:10](=[O:11])[CH:12]=[CH:31][CH:28]1[CH2:27][CH2:26][CH:25]([CH:24]([N:22]([CH3:21])[CH3:23])[C:33]2[CH:38]=[CH:37][CH:36]=[C:35]([F:39])[CH:34]=2)[CH2:30][CH2:29]1)[CH3:7]

Participants

5

Reactant 3

HCID 13345Triethyl phosphonoacetateHCID 23665647Potassium tert-butoxideHCID 866278884-[Dimethylamino-(3-fluorophenyl)-methyl]-cyclohexane-carbaldehyde

Product 1

HCID 669935943-{4-[Dimethylamino-(3-fluorophenyl)-methyl]-cyclohexyl}-acrylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Potassium tert-butylate (12.34 g, 0.11 mol) was added, under argon, to a solution of phosphonoacetic acid triethyl ester (24.66 g, 0.11 mol) in abs. DMF (200 ml), and the mixture was stirred for 10 minutes. The aldehyde 34 (19.3 g, 0.073 mol) dissolved in DMF (200 ml) was then added dropwise. The mixture was stirred for 3 h at RT and then poured onto ice. The reaction mixture was extracted with diethyl ether (3×200 ml) and the organic phase was washed with water and saturated NaCl solution, dried and concentrated in vacuo. The crude product was purified by flash chromatography with ethyl acetate/cyclohexane (1:2).

Workup

  1. additionwas then added dropwise
  2. additionpoured onto ice
  3. extractionThe reaction mixture was extracted with diethyl ether (3×200 ml)
  4. washthe organic phase was washed with water and saturated NaCl solution
  5. customdried
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by flash chromatography with ethyl acetate/cyclohexane (1:2)

Sources & evidence

ORD record
ord-a86af96da364407fbdb48b17d62f1ca1
Source dataset
uspto-grants-2011_11
Patent number
US08058475B2

Reaction notes

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