Toluene → HCID 68153913, compound

HRID 2039378Notes

Reaction equation

HRID 2039378 reaction equation
[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[CH:14][C:13]([CH:16]=O)=[CH:12][CH:11]=2)=[C:6]([F:18])[C:5]=1[F:19])[CH3:2].C(OP([CH2:28][C:29]([O:31][CH2:32][CH3:33])=[O:30])(OCC)=O)C.C1(C)C=CC=CC=1.[O-]CC.[Na+]>C(O)C.O>[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[CH:14][C:13]([CH2:16][CH2:28][C:29]([O:31][CH2:32][CH3:33])=[O:30])=[CH:12][CH:11]=2)=[C:6]([F:18])[C:5]=1[F:19])[CH3:2]

Participants

7

Reactant 4

HCID 1140TolueneHCID 13345Triethyl phosphonoacetateHCID 2723922Sodium ethoxideHCID 86668462HCID 86668462, compound

Product 1

HCID 68153913HCID 68153913, compoundYield 75.6%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

4-Ethoxy-4′-formyl-2,3-difluoro-1,1′-biphenyl (s49) (30.0 g), ethyl diethylphosphonoacetate (30.8 g) and toluene (200 ml) were placed in a reaction vessel under an atmosphere of nitrogen, and cooled to 0° C. Sodium ethoxide in ethanol solution (20%; 46.7 g) was added at the same temperature, and the stirring was continued for another 2 hours. After the reaction mixture had been returned to 25° C., the stirring was continued for another 2 hours. The reaction mixture was treated with water, and the aqueous layer was extracted with toluene. The combined organic layers were washed with water, and then dried over anhydrous magnesium sulfate. The solution was concentrated under reduced pressure, and the residue was purified by column chromatography with a mixed solvent of toluene and heptane (toluene:heptane=2:1 by volume) as an eluent and silica gel as a stationary phase powder. The purified product was dissolved in 2-propanol (150 ml), to which Pd/C (1.5 g) was added. The mixture was stirred at room temperature under a hydrogen atmosphere until hydrogen absorption had ceased. After the reaction had been completed, Pd/C was removed, and then solvent was distilled off. The residue was purified by column chromatography with toluene as an eluent and silica gel as a stationary phase powder to give ethyl 3-(4′-ethoxy-2′,3′-difluoro-(1,1′-biphenyl)-4-yl)propionate (s50) (28.9 g). The yield based on the compound (s49) was 75.6%.

Workup

  1. customhad been returned to 25° C.
  2. waitthe stirring was continued for another 2 hours
  3. extractionthe aqueous layer was extracted with toluene
  4. washThe combined organic layers were washed with water
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationThe solution was concentrated under reduced pressure
  7. customthe residue was purified by column chromatography with a mixed solvent of toluene and heptane (toluene:heptane=2:1 by volume) as an eluent
  8. dissolutionThe purified product was dissolved in 2-propanol (150 ml), to which Pd/C (1.5 g)
  9. additionwas added
  10. customPd/C was removed
  11. distillationsolvent was distilled off
  12. customThe residue was purified by column chromatography with toluene as an eluent

Sources & evidence

ORD record
ord-f489f40c715d4d7c994588c65fa3d8f4
Source dataset
uspto-grants-2013_11
Patent number
US08580146B2

Reaction notes

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