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Hexamethyldisilazane → (R)-4-benzyl-3-((R)-2-((1-(3-methoxypropyl)-1H-indazol-6-yl)methyl)-3-methylbutanoyl)-oxazolidin-2-one

HRID 660368
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 660368
C[Si](C)(C)N[Si](C)(C)C.[Li]CCCC.[CH2:15]([C@@H:22]1[CH2:26][O:25][C:24](=[O:27])[N:23]1[C:28](=[O:33])[CH2:29][CH:30]([CH3:32])[CH3:31])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.Br[CH2:35][C:36]1[CH:44]=[C:43]2[C:39]([CH:40]=[N:41][N:42]2[CH2:45][CH2:46][CH2:47][O:48][CH3:49])=[CH:38][CH:37]=1.[NH4+].[Cl-]>C1COCC1>[CH2:15]([C@@H:22]1[CH2:26][O:25][C:24](=[O:27])[N:23]1[C:28](=[O:33])[C@H:29]([CH2:35][C:36]1[CH:44]=[C:43]2[C:39]([CH:40]=[N:41][N:42]2[CH2:45][CH2:46][CH2:47][O:48][CH3:49])=[CH:38][CH:37]=1)[CH:30]([CH3:31])[CH3:32])[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1
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Komponenten

7

Edukt 5

HCID 13838HexamethyldisilazaneHCID 25517Ammonium ChlorideHCID 11391340(4R)-4-Benzyl-3-(3-methylbutanoyl)-1,3-oxazolidin-2-oneHCID 687838246-(bromomethyl)-1-(3-methoxypropyl)-1H-indazoleHCID 178418339Butyllithium

Produkt 1

HCID 68786317
(R)-4-benzyl-3-((R)-2-((1-(3-methoxypropyl)-1H-indazol-6-yl)methyl)-3-methylbutanoyl)-oxazolidin-2-one
Ausbeute 49 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel3×

Versuchsvorschrift

To a stirred solution of hexamethyldisilazane (200 mg, 1.24 mmol) in anhydrous THF (2 mL) cooled to −78° C. under N2 was added dropwise 2.5 M n-BuLi (0.5 mL, 1.25 mol) over 30 min. After stirring for an additional 30 min, a solution of (R)-4-benzyl-3-(3-methylbutanoyl)oxazolidin-2-one (313 mg, 1.2 mmol) in THF (2 mL) was added dropwise to the reaction mixture. The mixture was stirred at −78° C. for 2 h and a solution of 6-(bromomethyl)-1-(3-methoxypropyl)-1H-indazole (300 mg, 1.1 mmol) in THF (2 mL) was added. The mixture was allowed to warm from −78° C. to 0° C. over 2 h and stirred at it for 18 h. 10% aq NH4Cl was added and the mixture was extracted with EtOAc (3×10 mL). The combined organic layers were washed with brine, dried over Na2SO4, and concentrated. The residue was purified by flash chromatography on silica gel to give (R)-4-benzyl-3-((R)-2-((1-(3-methoxypropyl)-1H-indazol-6-yl)methyl)-3-methylbutanoyl)-oxazolidin-2-one (250 mg, 49%). 1H NMR (400 MHz, CDCl3): 1.09 (m, 6H), 1.96 (m, 1H), 2.09 (m, 3H), 2.61 (m, 1H), 3.12 (m, 2H), 3.22 (m, 2H), 3.29 (s, 3H), 3.89 (m, 1H), 4.02 (m, 1H), 4.35 (m, 1H), 4.40 (m, 1H), 4.59 (m, 1H), 6.75 (m, 2H), 7.07 (m, 3H), 7.13 (m, 1H), 7.26 (m, 1H), 7.33 (m, 1H), 7.61 (m, 1H), 7.91 (m, 1H); MS: 464 (M++1)

Aufarbeitung

  1. stirringThe mixture was stirred at −78° C. for 2 h
  2. temperatureto warm from −78° C. to 0° C. over 2 h
  3. stirringstirred at it for 18 h
  4. extractionthe mixture was extracted with EtOAc (3×10 mL)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customThe residue was purified by flash chromatography on silica gel

Quellen und Nachweise

ORD-Eintrag
ord-b909c1a4ba1140f49675c957a2b5003d
Quelldatensatz
uspto-grants-2011_12
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08084485B2

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