Water → Trans-N-Boc-2-(4-chlorophenyl)-3-(isopropylamino) acrylic acid

HRID 922169Notes

Reaction equation

HRID 922169 reaction equation
[C:1]([O:5][C:6]([N:8]([CH:23]([CH3:25])[CH3:24])/[CH:9]=[C:10](\[C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=1)/[C:11]([O:13]CC)=[O:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].O.[OH-].[Na+]>CCO>[C:1]([O:5][C:6]([N:8]([CH:23]([CH3:25])[CH3:24])/[CH:9]=[C:10](\[C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=1)/[C:11]([OH:13])=[O:12])=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

5

Reactant 3

HCID 962WaterHCID 14798Sodium HydroxideHCID 118084365HCID 118084365, compound

Product 1

HCID 89905140Trans-N-Boc-2-(4-chlorophenyl)-3-(isopropylamino) acrylic acidYield 90.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

(E)-ethyl 3-((tert-butoxycarbonyl)(isopropyl)amino)-2-(4-chlorophenyl)acrylate (133.5 kg, 362.9 mol) was added into a mixture of H2O (252 L), NaOH (58.25 kg, 1456 mol) and EtOH (383.5 L) stirred at room temperature. The mixture was warmed to 40-45° C. for 2.5 h until a clear solution was formed. The mixture was concentrated to a minimum working volume maintaining the temperature below 50° C. The mixture was then cooled to 10-25° C. and a solution of HCl was added (842 L of 2N HCl and 11 L of 35% HCl) until a final pH=2˜4 was obtained. The aqueous layer was separated and the organic layer was washed with 25% aqueous NaCl (810 L). n-Heptane was added while distilling to form a suspension. The product was collected and washed with n-heptane and dried at 40-45° C. for ˜10 h to afford 110.7 kg (90.5% yield) of (E)-3-(tert-butoxycarbonyl(isopropyl)amino)-2-(4-chlorophenyl)acrylic acid having 99.9 A % purity by HPLC. E-configuration was confirmed using single crystal x-ray analysis (See FIG. 1).

Workup

  1. temperatureThe mixture was warmed to 40-45° C. for 2.5 h until a clear solution
  2. customwas formed
  3. concentrationThe mixture was concentrated to a minimum working volume
  4. temperaturemaintaining the temperature below 50° C
  5. temperatureThe mixture was then cooled to 10-25° C.
  6. additiona solution of HCl was added (842 L of 2N HCl and 11 L of 35% HCl) until a final pH=2˜4
  7. customwas obtained
  8. customThe aqueous layer was separated
  9. washthe organic layer was washed with 25% aqueous NaCl (810 L)
  10. additionn-Heptane was added
  11. distillationwhile distilling
  12. customto form a suspension
  13. customThe product was collected
  14. washwashed with n-heptane
  15. customdried at 40-45° C. for ˜10 h

Sources & evidence

ORD record
ord-255c4eb61db14172b61664b00cbfb517
Source dataset
uspto-grants-2016_03
Patent number
US09278917B2

Reaction notes

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