Acetic Acid → HCID 14023756, compound

HRID 425955Notes

Reaction equation

HRID 425955 reaction equation
[CH:1](=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[CH2:10][C:11]([O:13]C)=O.[CH3:15][O-:16].[Na+].C(O)(=[O:20])C.[BrH:22].C(=O)(O)[O-].[Na+]>CO.O.C1(C)C=CC=CC=1>[CH3:15][O:16][C:11](=[O:13])[CH:10]([OH:20])[CH:1]([Br:22])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

10

Reactant 6

HCID 176Acetic AcidHCID 240BenzaldehydeHCID 260Hydrogen BromideHCID 7295Methyl chloroacetateHCID 516892Sodium BicarbonateHCID 10942334Sodium Methoxide

Product 1

HCID 14023756HCID 14023756, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 962WaterSolvent2×HCID 1140TolueneSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of benzaldehyde (212.0 g, 2.0 moles) and methyl chloroacetate (282.0 g, 2.6 mole) in methanol (320.0 g) was cooled to 0° C. under nitrogen. Sodium methoxide (466.0 g of a 30 wt % solution in methanol, 2.5 moles) was added over a period of 2 hours and the mixture was stirred for further 60 minutes at 0° C. The mixture was then allowed to reach 22° C. and stirred for further 2 hours at this temperature. After slow addition of acetic acid (30.0 g, 0.5 moles), toluene (465.0 g) and water (670.0 g) were added consecutively. The aqueous phase was separated and the organic layer was distilled in order to remove water and methanol. After removal of 170.0 g of distillate the mixture was allowed to cool to 25° C. HBr (120.0 g, 1.5 moles) was added over a period of 4 hours keeping the temperature at 25° C. After completion of the addition a mixture of 15.0 g of sodium bicarbonate in 300.0 g water was added dropwise, keeping the temperature between 25 and 30° C. The aqueous layer was then separated, toluene (175.0 g) was added and 115.0 g of toluene was distilled off in order to remove moisture. The mixture was cooled down to 20° C. and toluene (115.0 g) and heptane (260.0 g) were added consecutively. After seeding with 0.5 g of racemic 3-bromo-2-hydroxy-3-phenyl-propionic acid methyl ester, the mixture was slowly cooled to 0° C. and stirred for further 3 hours. The precipitated product was filtered off, washed with 200.0 g heptane and vacuum dried at 45° C. Yield: 234.0 g (0.9 mole, 45%).

Workup

  1. customto reach 22° C.
  2. stirringstirred for further 2 hours at this temperature
  3. additionwere added consecutively
  4. customThe aqueous phase was separated
  5. distillationthe organic layer was distilled in order
  6. customto remove water and methanol
  7. customAfter removal of 170.0 g of distillate the mixture
  8. temperatureto cool to 25° C
  9. customat 25° C
  10. additionAfter completion of the addition
  11. additionwas added dropwise
  12. customthe temperature between 25 and 30° C
  13. customThe aqueous layer was then separated
  14. additiontoluene (175.0 g) was added
  15. distillation115.0 g of toluene was distilled off in order
  16. customto remove moisture
  17. temperatureThe mixture was cooled down to 20° C.
  18. additiontoluene (115.0 g) and heptane (260.0 g) were added consecutively
  19. temperaturethe mixture was slowly cooled to 0° C.
  20. stirringstirred for further 3 hours
  21. filtrationThe precipitated product was filtered off
  22. washwashed with 200.0 g heptane and vacuum
  23. customdried at 45° C

Sources & evidence

ORD record
ord-0951bbbec3e549e8ad0140470b04fa3d
Source dataset
uspto-grants-2012_01
Patent number
US08106231B2

Reaction notes

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