Acetic Acid → L-Aspartic Acid

HRID 1489832Notes

Reaction equation

HRID 1489832 reaction equation
[OH-:1].[Na+].C(=O)(O)[O-].[Na+].ClC([O:11][CH2:12][C:13](Cl)(Cl)Cl)=O.[NH3:17].[C:18]([OH:21])(=[O:20])[CH3:19]>CC(C)=O.C(Cl)Cl.O1CCOCC1>[NH2:17][C@H:13]([C:12]([OH:11])=[O:1])[CH2:19][C:18]([OH:21])=[O:20]

Participants

9

Reactant 5

HCID 176Acetic AcidHCID 222AmmoniaHCID 14798Sodium HydroxideHCID 870632,2,2-Trichloroethyl chloroformateHCID 516892Sodium Bicarbonate

Product 1

HCID 5960L-Aspartic AcidYield 75%

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 8.2 mL of aqueous sodium hydroxide (1M, 8.2 mmol) and 16.4 mL of aqueous sodium bicarbonate (1M, 16.4 mmol) was added to the b-(p-methoxybenzoate) aspartic acid D (2.1 g, 8.2 mmol). (W. A. R. van Heeswijk, et al., Synthesis, 1982, 744) 16 mL of dioxane was added to dissolve the white paste and 2,2,2-trichloroethyl chloroformate (TrocCl, 1.24 mL, 9.03 mmol) was slowly added. Evolution of gas was observed and the mixture was stirred for 6 h. The solution was then extracted with ethyl acetate (3×100 mL), the aqueous layer was acidified with concentrated HCl and was extracted with ethyl acetate (2×100 mL). The organic extracts were combined, washed with 100 mL of brine, dried with sodium sulfate and the solvents were removed under reduced pressure. The residue was purified on silica [100 g, 80:19:1 CH2Cl2 : acetone:acetic acid→10:29:1] to give E (2.63 g, 75% yield). Rf =0.3 [80:19:1 CH2Cl2 :acetone:acetic acid]; FTIR (neat); 3327 (OH), 2958, 1732, 1516, 1248; 1H NMR (400 MHz) d 10-9 (br s, 1H, COOH), 7.28 (d, 2H, J=8 Hz, PMB), 6.89 (d, 2H, J=8 Hz, PMB), 6.01 (br d, 2H, J=8 Hz, NH), 5.15-5.05 (m, 2H, PMB), 4.8-4.6 (m, 3H), 3.81 (s, 3H, OMe), 3.13 (dd, 1H, J=17 Hz, J=4 Hz, Hb Asn), 2.93 (dd, 1H, J=17 Hz, J=5 Hz, Hb Asn); 13C d 175.12, 170.72, 159.63, 154.35, 130.11 (2 C), 127.07, 113.92 (2 C), 95.05, 74.65, 66.95, 55.14, 50.26, 36.16; MS (DCI, NH3) m/z 427 (M+).

Workup

  1. additionwas added
  2. additionwas slowly added
  3. extractionThe solution was then extracted with ethyl acetate (3×100 mL)
  4. extractionwas extracted with ethyl acetate (2×100 mL)
  5. washwashed with 100 mL of brine
  6. dry with materialdried with sodium sulfate
  7. customthe solvents were removed under reduced pressure
  8. customThe residue was purified on silica [100 g, 80:19:1 CH2Cl2 : acetone:acetic acid→10:29:1]
  9. customto give E (2.63 g, 75% yield)

Sources & evidence

ORD record
ord-cbfd6e87aaab46a4b92228704c151a85
Source dataset
uspto-grants-1997_10
Patent number
US05679769

Reaction notes

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