Diisopropylethylamine → (2R)-4-[3-(2-fluoro-3-methoxyphenyl)isoxazol-5-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

HRID 404218Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 404218
C(N(C(C)C)C(C)C)C.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.[F:28][C:29]1[C:34]([O:35][CH3:36])=[CH:33][CH:32]=[CH:31][C:30]=1[C:37]1[CH:41]=[C:40]([CH2:42][CH2:43][C@@:44]([CH3:52])([S:48]([CH3:51])(=[O:50])=[O:49])[C:45](O)=[O:46])[O:39][N:38]=1.[O:53]1[CH2:58][CH2:57][CH2:56][CH2:55][CH:54]1[O:59][NH2:60]>CN(C1C=CN=CC=1)C.C(OCC)(=O)C.O>[F:28][C:29]1[C:34]([O:35][CH3:36])=[CH:33][CH:32]=[CH:31][C:30]=1[C:37]1[CH:41]=[C:40]([CH2:42][CH2:43][C@@:44]([CH3:52])([S:48]([CH3:51])(=[O:49])=[O:50])[C:45]([NH:60][O:59][CH:54]2[CH2:55][CH2:56][CH2:57][CH2:58][O:53]2)=[O:46])[O:39][N:38]=1

Komponenten

8

Edukt 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 70817723(2R)-4-[3-(2-Fluoro-3-methoxyphenyl)isoxazol-5-yl]-2-methyl-2-(methylsulfonyl)butanoic acid

Produkt 1

HCID 86709151(2R)-4-[3-(2-fluoro-3-methoxyphenyl)isoxazol-5-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamideAusbeute 44,4 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittel2×

Versuchsvorschrift

N,N-Dimethy-4-aminopyridine (0.04 g, 0.3 mmol, 0.3 equiv), N-ethyl-N-isopropylpropan-2-amine (0.89 mL, 5.2 mmol, 4.5 equiv), T3P® (50% w/w solution in ethyl acetate, 2.7 mL, 4.5 mmol, 4.0 equiv), and (2R)-4-[3-(2-fluoro-3-methoxyphenyl)isoxazol-5-yl]-2-methyl-2-(methylsulfonyl)butanoic acid (0.42 g, 1.1 mmol, 1.0 equiv) were allowed to stir at room temperature for 30 min. A solution of O-(tetrahydro-2H-pyran-2-yl)hydroxylamine (0.15 g, 1.2 mmol, 1.2 equiv) in ethyl acetate (12 mL) was added, and the reaction was allowed to stir overnight (18 h) at room temperature. Water (40 mL) was added, and the mixture was extracted with ethyl acetate (2×50 mL). The combined organic phases were dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography (25 g silica gel column, 0-100% gradient ethyl acetate in hexanes) to provide (2R)-4-[3-(2-fluoro-3-methoxyphenyl)isoxazol-5-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide as a tan solid (0.23 g, 42%). MS (LCMS) m/z 469.1 (M−1).

Aufarbeitung

  1. stirringto stir overnight (18 h) at room temperature
  2. extractionthe mixture was extracted with ethyl acetate (2×50 mL)
  3. dry with materialThe combined organic phases were dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude material was purified by flash chromatography (25 g silica gel column, 0-100% gradient ethyl acetate in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-5241cba5a0204e5d90b85f29e62c6038
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08748466B2

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