Trifluoroacetic acid → HCID 60150642, Verbindung

HRID 2277103Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2277103
C([O-])([O-])=O.[K+].[K+].C([O:10][C@H:11]([C:40]([CH3:43])([CH3:42])[CH3:41])[C:12]([N:14]1[CH2:19][CH2:18][S:17][CH2:16][C@H:15]1[C:20](=[O:39])[NH:21][CH2:22][C:23]1[CH:28]=[C:27]([Cl:29])[CH:26]=[CH:25][C:24]=1[CH2:30][NH:31]C(OC(C)(C)C)=O)=[O:13])(=O)C.[F:44][C:45]([F:50])([F:49])[C:46]([OH:48])=[O:47]>CO.CCOC(C)=O.C(Cl)Cl>[F:44][C:45]([F:50])([F:49])[C:46]([OH:48])=[O:47].[NH2:31][CH2:30][C:24]1[CH:25]=[CH:26][C:27]([Cl:29])=[CH:28][C:23]=1[CH2:22][NH:21][C:20]([C@@H:15]1[CH2:16][S:17][CH2:18][CH2:19][N:14]1[C:12](=[O:13])[C@H:11]([OH:10])[C:40]([CH3:43])([CH3:42])[CH3:41])=[O:39]

Komponenten

7

Edukt 3

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 89825002HCID 89825002, Verbindung

Produkt 1

HCID 60150642HCID 60150642, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 887MethanolLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

Solid K2CO3 (5.8 mg, 0.042 mmol) was added to the solution of (R)-1-{(R)-3-[2-{(tert-Butoxycarbonylamino)methyl}-5-chlorobenzylcarbamoyl]thiomorpholino)-3,3-dimethyl-1-oxo-butan-2-yl acetate (0.12 g, 0.21 mmol) in MeOH (5 mL) and the reaction mixture was stirred at room temperature for 30 min. The reaction mixture was diluted with EtOAc (50 mL) and washed with 0.1M aqueous HCl (20 mL), water (2×20 mL), and brine solution (20 mL). The organic layer was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by reverse phase combiflash column chromatography (C18; eluent: 10-100% acetonitrile/water) to afford the intermediate BOC-protected alcohol as an off-white solid (0.092 g, crude). The crude intermediate was dissolved in CH2Cl2 (3 mL) then trifluoroacetic acid (1.0 mL, 13.42 mmol) was added and the resulting mixture was stirred at room temperature for 2 h. Volatile byproducts were removed under vacuum and the residue was purified by reverse phase combiflash column chromatography (C18; eluent: 10-100% acetonitrile:water) to afford the title compound as a white solid. 1H NMR (MeOD 400 MHZ) (δ) ppm: 7.41 (s, 1H); 7.39-7.35 (m, 2H); 5.28 (t, J=4.4 Hz, 1H); 4.54-4.38 (m, 3H); 4.28-4.21 (m, 3H); 3.61-3.54 (m, 1H); 3.18-3.12 (m, 1H); 2.93-2.88 (m, 1H); 2.82-2.75 (m, 1H); 2.62-2.59 (m, 1H), 0.98 (m, 9H).

Aufarbeitung

  1. washwashed with 0.1M aqueous HCl (20 mL), water (2×20 mL), and brine solution (20 mL)
  2. dry with materialThe organic layer was dried over anhydrous Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by reverse phase combiflash column chromatography (C18; eluent: 10-100% acetonitrile/water)
  6. customto afford the intermediate BOC-protected alcohol as an off-white solid (0.092 g, crude)
  7. stirringthe resulting mixture was stirred at room temperature for 2 h
  8. customVolatile byproducts were removed under vacuum
  9. customthe residue was purified by reverse phase combiflash column chromatography (C18; eluent: 10-100% acetonitrile:water)

Quellen und Nachweise

ORD-Eintrag
ord-cc5c3c23b2bb46a5b3c97d7a9b12f0d5
Quelldatensatz
uspto-grants-2015_09
Patentnummer
US09133147B2

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