Sodium hydride → HCID 178459923, Verbindung

HRID 1766887Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1766887
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@:9]([OH:38])([CH2:32][N:33]1[CH:37]=[N:36][CH:35]=[N:34]1)[C@H:10]([S:12][C@@H:13]1[CH2:18][O:17][C@@H:16](/[CH:19]=[CH:20]/[CH:21]=[CH:22]/[C:23]2[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[CH:25][C:24]=2[F:31])[O:15][CH2:14]1)[CH3:11].[H-].[Na+].[CH2:41]([O:44][C:45]([O:47][CH2:48][CH2:49][CH2:50][C:51](Cl)=[O:52])=[O:46])[CH:42]=[CH2:43].[Cl-].[NH4+]>CN(C)C=O.C(OCC)(=O)C>[CH2:41]([O:44][C:45]([O:47][CH2:48][CH2:49][CH2:50][C:51]([O:38][C@:9]([C:3]1[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=1[F:1])([CH2:32][N:33]1[CH:37]=[N:36][CH:35]=[N:34]1)[C@H:10]([S:12][C@@H:13]1[CH2:18][O:17][C@@H:16](/[CH:19]=[CH:20]/[CH:21]=[CH:22]/[C:23]2[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[CH:25][C:24]=2[F:31])[O:15][CH2:14]1)[CH3:11])=[O:52])=[O:46])[CH:42]=[CH2:43]

Komponenten

7

Edukt 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 178625384-(Allyloxycarbonyloxy)butyryl chlorideHCID 178462432HCID 178462432, Verbindung

Produkt 1

HCID 178459923HCID 178459923, VerbindungAusbeute 75,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

4-[(1E,3E)-4-[trans-5-[[(1R,2R)-2-(2,4-Difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]thio]-1,3-dioxan-2-yl]-1,3-butadienyl]-3-fluorobenzonitrile (570 mg, 1.05 mmol) obtained from Example Reference example 1 was dissolved in N,N-dimethylformamide (3 ml), and sodium hydride (ca. 30 mg, 1.3 mmol) was added thereto at room temperature. The mixture was stirred for 1 hour, then 4-(allyloxycarbonyloxy)butyryl chloride (250 mg, 1.21 mmol) obtained from Example 11-(2) was added thereto, and the mixture was stirred further for 1 hour. The mixture was diluted with ethyl acetate, and a saturated aqueous solution of ammonium chloride was poured thereinto. The organic layer was separated, washed with an aqueous solution of sodium hydrogen carbonate and then with an aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by recycle preparative HPLC [LC-908; Japan Analytical Industry Co., Ltd.; GPC column JAIGEL-1H (20 mm i.d.×600 mm) and JAIGEL-2H (20 mm i.d.×600 mm) connected in series for use; solvent, chloroform] to afford the title compound (562 mg, 75% yield) as a colorless amorphous solid.

Aufarbeitung

  1. customat room temperature
  2. stirringthe mixture was stirred further for 1 hour
  3. customThe organic layer was separated
  4. washwashed with an aqueous solution of sodium hydrogen carbonate
  5. dry with materialwith an aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate
  6. distillationthe solvent was distilled off under reduced pressure
  7. customThe residue was purified by recycle preparative HPLC [LC-908; Japan Analytical Industry Co., Ltd.; GPC column JAIGEL-1H (20 mm i.d.×600 mm) and JAIGEL-2H (20 mm i.d.×600 mm) connected in series for use; solvent, chloroform]

Quellen und Nachweise

ORD-Eintrag
ord-b5513773b2ee4d04bc932eae3c057479
Quelldatensatz
uspto-grants-2007_06
Patentnummer
US07230023B2

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