Methanesulfonic Acid → (2R)-2-phenylcarbonyloxypropyl (2S)-2-amino-3-(3,4-dihydroxyphenyl)propanoate mesylate

HRID 1023754

Reaktionsgleichung

Reaktionsgleichung von HRID 1023754
C([O-])(O)=O.[Na+].Cl.[NH2:7][C@@H:8]([CH2:24][C:25]1[CH:30]=[CH:29][C:28]([OH:31])=[C:27]([OH:32])[CH:26]=1)[C:9]([O:11][CH2:12][C@H:13]([O:15][C:16]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:17])[CH3:14])=[O:10].[CH3:33][S:34]([OH:37])(=[O:36])=[O:35].C(OCC)(=O)C>O>[S:34]([OH:37])(=[O:36])(=[O:35])[CH3:33].[NH2:7][C@@H:8]([CH2:24][C:25]1[CH:30]=[CH:29][C:28]([OH:31])=[C:27]([OH:32])[CH:26]=1)[C:9]([O:11][CH2:12][C@H:13]([O:15][C:16]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:17])[CH3:14])=[O:10]

Komponenten

6

Edukt 4

HCID 6395Methanesulfonic Acid2×HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 11582017(2R)-2-Phenylcarbonyloxypropyl (2S)-2-Amino-3-(3,4-dihydroxyphenyl)propanoate Hydrochloride

Produkt 1

HCID 16125134(2R)-2-phenylcarbonyloxypropyl (2S)-2-amino-3-(3,4-dihydroxyphenyl)propanoate mesylateAusbeute 99,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel2×

Versuchsvorschrift

A solution of NaHCO3 (9.87 g, 117.5 mmol) in water (80 mL) was slowly added to a solution of hydrochloride salt 1d (31.0 g, 78.3 mmol) in water (300 mL). The resulting aqueous suspension was extracted with ethyl acetate (EtOAc) (2×400 mL). The combined EtOAc extract was washed with water, then brine, and dried through MgSO4. Methanesulfonic acid (6.04 mL, 93.12 mmol) was slowly added to the ethyl acetate (EtOAc) solution while stirred. White precipitate formed as soon as the addition of methanesulfonic acid was complete. The suspension was stirred for another 30 min and then filtered. The filter cake was washed three times with ethyl acetate (EtOAc) and vacuum dried overnight to afford 35.4 g (quantitative yield) of anhydrous mesylate salt 1 as a white solid. 1H NMR (400 MHz, CD3OD): δ 1.40 (d, J=6.4 Hz, 3H), 2.70 (s, 3H), 2.98 (dd, J=7.8, 14.6 Hz, 1H), 3.10 (dd, J=5.6, 14.4 Hz, 1H), 4.24 (dd, J=5.8, 7.8 Hz, 1H), 4.38 (dd, J=6.8, 12.0 Hz, 1H), 4.52 (dd, J=3.4, 11.8 Hz, 1H), 5.40 (dp, J=3.2, 6.4 Hz, 1H), 6.52 (dd, J=2.2, 8.2 Hz, 1H), 6.67 (d, J=2.2 Hz, 1H), 6.69 (d, J=8.0 Hz, 1H), 7.47 (t, J=7.6 Hz, 2H), 7.60 (br t, J=7.4 Hz, 1H), 8.01 (d, J=7.6 Hz, 2H). MS (ESI) m/z 360.07 (M+H)+ and 358.01 (M−H)−.

Aufarbeitung

  1. extractionThe resulting aqueous suspension was extracted with ethyl acetate (EtOAc) (2×400 mL)
  2. extractionThe combined EtOAc extract
  3. washwas washed with water
  4. dry with materialbrine, and dried through MgSO4
  5. customWhite precipitate
  6. customformed as
  7. stirringThe suspension was stirred for another 30 min
  8. filtrationfiltered
  9. washThe filter cake was washed three times with ethyl acetate (EtOAc) and vacuum
  10. customdried overnight

Quellen und Nachweise

ORD-Eintrag
ord-4396d078c7214c1484d23d5d4550129e
Quelldatensatz
uspto-grants-2014_05
Patentnummer
US08722733B2

Verknüpfte Notizen

Wird geladen…