Trifluoroacetic acid → N-{(1R,2R)-2-[4-(6-Ethylaminomethyl-pyridin-3-yl)-phenyl]-1-fluoromethyl-2-hydroxy-ethyl}-2,2-difluoro-acetamide

HRID 1487480Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1487480
[CH2:1]([NH:3][CH2:4][C:5]1[N:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][C:14]([C@H:17]3[O:21]C(C)(C)[N:19]([C:24](=[O:28])[CH:25]([F:27])[F:26])[C@@H:18]3[CH2:29][F:30])=[CH:13][CH:12]=2)=[CH:7][CH:6]=1)[CH3:2].FC(F)(F)C(O)=O>C(Cl)Cl.C(=O)(O)[O-]>[CH2:1]([NH:3][CH2:4][C:5]1[N:10]=[CH:9][C:8]([C:11]2[CH:12]=[CH:13][C:14]([C@@H:17]([OH:21])[C@@H:18]([NH:19][C:24](=[O:28])[CH:25]([F:26])[F:27])[CH2:29][F:30])=[CH:15][CH:16]=2)=[CH:7][CH:6]=1)[CH3:2]

Komponenten

5

Edukt 2

HCID 6422Trifluoroacetic acidHCID 866954361-{(4S,5R)-5-[4-(6-Ethylaminomethyl-pyridin-3-yl)-phenyl]-4-fluoromethyl-2,2-dimethyl-oxazolidin-3-yl}-2,2-difluoro-ethanone

Produkt 1

HCID 86695437N-{(1R,2R)-2-[4-(6-Ethylaminomethyl-pyridin-3-yl)-phenyl]-1-fluoromethyl-2-hydroxy-ethyl}-2,2-difluoro-acetamideAusbeute 62,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 769Bicarbonate IonLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of 1-{(4S,5R)-5-[4-(6-Ethylaminomethyl-pyridin-3-yl)-phenyl]-4-fluoromethyl-2,2-dimethyl-oxazolidin-3-yl}-2,2-difluoro-ethanone (0.062 g, 0.147 mmol) in CH2Cl2 (5 mL) is added trifluroacetic acid (1.0 mL) at room temperature. The resulting reaction mixture is stirred at room temperature for 5 hours. Solvent is evaporated in vacuo to get the crude residue and diluted with aqueous bicarbonate solution and extracted with ethyl acetate. Organic layer is dried over sodium sulphate, concentrated and purified by combi-flash chromatography using 15% methanol in CH2Cl2 as an eluent. Obtained solid is washed with n-pentane and diethyl ether to afford the title compound (0.035 g) after drying in lypholizer. 1H NMR (400 MHz, DMSO-d6) δ: 1.16 (t, J=7.2 Hz, 3H), 2.83-2.88 (q, 2H), 4.14 (s, 2H), 4.30-4.33 (m, 1.5H), 4.41-4.45 (m, 0.5H), 4.55-4.56 (m, 0.5H), 4.65-4.68 (m, 0.5H), 4.89 (t, J=4.08 Hz, 1H), 5.93 (d, J=4.55 Hz, 1H), 6.20 (t, J=53.76 Hz, 1H), 7.47 (d, J=8.24 Hz, 2H), 7.54 (d, J=8.2 Hz, 1H), 7.72 (d, J=8.24 Hz, 2H), 8.12-8.15 (dd, J1=2.32 Hz, J2=8.16 Hz, 1H), 8.85 (d, J=8.8 Hz, 1H), 8.90 (d, J=2.12 Hz, 1H). LC-MS (m/z): [M+H]=382.1.

Aufarbeitung

  1. customThe resulting reaction mixture
  2. customSolvent is evaporated in vacuo
  3. customto get the crude residue
  4. extractionextracted with ethyl acetate
  5. dry with materialOrganic layer is dried over sodium sulphate
  6. concentrationconcentrated
  7. custompurified by combi-flash chromatography
  8. customObtained solid
  9. washis washed with n-pentane and diethyl ether

Quellen und Nachweise

ORD-Eintrag
ord-aff72b5cb2114fea8da24647b905c193
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09428528B2

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