Sulfuric Acid → Dimethyl 3-aminopentanedioate

HRID 1946988Notes

Reaction equation

HRID 1946988 reaction equation
[S:1](=[O:5])(=[O:4])([OH:3])[OH:2].CC(O)C.B.C(N)(C)(C)C.[CH3:16][O:17][C:18](=[O:27])[CH:19]=[C:20]([NH2:26])[CH2:21][C:22]([O:24][CH3:25])=[O:23]>C1COCC1>[S:1](=[O:3])(=[O:2])([OH:5])[OH:4].[CH3:25][O:24][C:22](=[O:23])[CH2:21][CH:20]([NH2:26])[CH2:19][C:18]([O:17][CH3:16])=[O:27]

Participants

7

Reactant 4

HCID 1118Sulfuric AcidHCID 3776IsopropanolHCID 253819Dimethyl 3-aminoglutaconateHCID 517393Borane;2-methylpropan-2-amine

Product 2

HCID 1118Sulfuric AcidHCID 253304Dimethyl 3-aminopentanedioateYield 97%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A diluted alcoholic sulfuric acid solution is prepared by adding sulfuric acid (20.69 Kg) to i-PrOH (51.7 Kg) at 0-5° C. The resulting solution was slowly added to a solution of tert-butylamine borane (9.19 Kg) in THF (69.3 Kg), maintaining the temperature below −5° C. Dimethyl-3-aminoglutaconate (18.28 Kg) was slowly added to the resulting mixture, maintaining the temperature below 0° C. The resulting reaction mixture was stirred between 0° C. and 15° C. overnight, then quenched by slow addition to water (166 Kg) while maintaining the temperature below 10° C. and the pH between 5 and 7 by adding concentrated aqueous NaOH. The pH of the mixture was then adjusted to about 9-10 by adding concentrated aqueous NaOH at the end of the quenching process. The phases were separated and the aqueous phase was extracted with DCM. The combined organic extracts were washed with brine (20.6 Kg), filtered through a cotton cartridge and concentrated under reduced pressure to give 3-amino-pentanedioic acid dimethyl ester (17.87 Kg, 97% yield).

Workup

  1. temperaturemaintaining the temperature below −5° C
  2. temperaturemaintaining the temperature below 0° C
  3. customThe resulting reaction mixture
  4. customquenched by slow addition to water (166 Kg)
  5. temperaturewhile maintaining the temperature below 10° C.
  6. additionthe pH between 5 and 7 by adding concentrated aqueous NaOH
  7. additionby adding concentrated aqueous NaOH at the end of the quenching process
  8. customThe phases were separated
  9. extractionthe aqueous phase was extracted with DCM
  10. washThe combined organic extracts were washed with brine (20.6 Kg)
  11. filtrationfiltered through a cotton cartridge
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-8d9f41bd5e2c40c1bb87e5e1ff4f59c8
Source dataset
uspto-grants-2013_03
Patent number
US08399462B2

Reaction notes

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