Hydrochloric Acid → N-(Methoxycarbonyl)-O-methyl-L-homoserine

HRID 1809322

Reaktionsgleichung

Reaktionsgleichung von HRID 1809322
[NH:1]1CCCCC1.[CH3:7][O:8][CH2:9][CH2:10][CH2:11][C:12]([OH:14])=[O:13].C([O-])([O-])=O.[Na+].[Na+].Cl[C:22]([O:24][CH3:25])=[O:23].Cl>CN(C=O)C>[CH3:7][O:8][CH2:9][CH2:10][C@H:11]([NH:1][C:22]([O:24][CH3:25])=[O:23])[C:12]([OH:14])=[O:13]

Komponenten

7

Edukt 5

HCID 313Hydrochloric AcidHCID 6586Methyl chloroformateHCID 8082PiperidineHCID 10340Sodium CarbonateHCID 922644-Methoxybutyric acid

Produkt 1

HCID 59610349N-(Methoxycarbonyl)-O-methyl-L-homoserineAusbeute 47,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

Piperidine (1.0 mL, 10 mmol) was added to a solution of (S)-2-(9H-fluoren-9-yl)methoxy)carbonylamino)-4-methoxybutanoic acid (0.355 g, 1 mmol) in DMF (3 mL), and the mixture was stirred at rt for 3 h. The volatiles were removed and the residue was partitioned between sat. NaHCO3 (aq.) (5 mL) and EtOAc (5 mL). The aqueous layer was further washed with EtOAc and Et2O. To the aqueous solution was added Na2CO3 (212 mg, 2.0 mmol) followed by methyl chloroformate (0.16 mL, 2.0 mmol) and the reaction mixture was stirred at rt for 16 h. The reaction mixture was acidified with 1 N HCl (aq.) until pH<7 and then extracted with EtOAc (2×10 mL). The combined organic layers were dried (Na2SO4), filtered and concentrated. The residue was purified by flash silica chromatography (EtOAc/hexanes, gradient from 20% to 70%) to yield (S)-4-methoxy-2-(methoxycarbonylamino)butanoic acid (Cap-194) (91.5 mg) as viscous colorless oil. LC-MS retention time=0.61 min; m/z 214 [M+Na]+. (Column: PHENOMENEX® Luna 3.0×50 mm S10. Solvent A=90% Water: 10% Methanol: 0.1% TFA. Solvent B=10% Water: 90% Methanol: 0.1% TFA. Flow Rate=4 mL/min. Start % B=0. Final % B=100. Gradient Time=3 min. Wavelength=220). 1H NMR (400 MHz, chloroform-d) δ ppm 7.41 (br. s., 1H), 5.74-6.02 (m, 1H), 4.32-4.56 (m, 1H), 3.70 (s, 3H), 3.54 (t, J=5.0 Hz, 2H), 3.34 (s, 3H), 1.99-2.23 (m, 2H).

Aufarbeitung

  1. customThe volatiles were removed
  2. customthe residue was partitioned between sat. NaHCO3 (aq.) (5 mL) and EtOAc (5 mL)
  3. washThe aqueous layer was further washed with EtOAc and Et2O
  4. stirringthe reaction mixture was stirred at rt for 16 h
  5. extractionextracted with EtOAc (2×10 mL)
  6. dry with materialThe combined organic layers were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by flash silica chromatography (EtOAc/hexanes, gradient from 20% to 70%)

Quellen und Nachweise

ORD-Eintrag
ord-83d1c6303fb64e479664a95cceb3575e
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08362020B2

Verknüpfte Notizen

Wird geladen…