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Sodium hydride → tert-butyl (2R,5R)-5-{[tert-butyl(dimethyl)silyl]oxy}-2-[2-(6-cyano-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)ethyl]piperidine-1-carboxylate

HRID 255352
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 255352
[Si:1]([O:8][C@H:9]1[CH2:14][N:13]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[C@@H:12]([CH2:22][CH2:23]O)[CH2:11][CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C(N(C(C)C)CC)(C)C.CS(Cl)(=O)=O.[O:39]=[C:40]1[NH:45][C:44]2[CH:46]=[C:47]([C:50]#[N:51])[CH:48]=[CH:49][C:43]=2[O:42][CH2:41]1.[H-].[Na+].S([O-])(=O)(=O)C>C(Cl)Cl.CN(C=O)C>[Si:1]([O:8][C@H:9]1[CH2:14][N:13]([C:15]([O:17][C:18]([CH3:21])([CH3:19])[CH3:20])=[O:16])[C@@H:12]([CH2:22][CH2:23][N:45]2[C:44]3[CH:46]=[C:47]([C:50]#[N:51])[CH:48]=[CH:49][C:43]=3[O:42][CH2:41][C:40]2=[O:39])[CH2:11][CH2:10]1)([C:4]([CH3:6])([CH3:5])[CH3:7])([CH3:3])[CH3:2]
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Komponenten

9

Edukt 6

HCID 24758Sodium hydrideHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 85257MethanesulfonateHCID 106548133-Oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carbonitrile2×HCID 66774126tert-butyl(2R,5R)-5-{[tert-butyl(dimethyl)silyl]oxy}-2-(2-hydroxyethyl)piperidine-1-carboxylate
2×

Produkt 1

HCID 66774834tert-butyl (2R,5R)-5-{[tert-butyl(dimethyl)silyl]oxy}-2-[2-(6-cyano-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)ethyl]piperidine-1-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

To a solution of tert-butyl (2R,5R)-5-{[tert-butyl(dimethyl)silyl]oxy}-2-(2-hydroxyethyl)piperidine-1-carboxylate (Intermediate 187, 1.27 g) in methylene chloride (15 mL) at 0° C. were added diisopropylethylamine (1.2 mL) and methanesulfonyl chloride (0.50 mL). At the same time in a separate flask, to a solution of 3-oxo-3,4-dihydro-2H-1,4-benzoxazine-6-carbonitrile (Intermediate 60) (0.66 g) in DMF (8 mL) at 0° C. was added 60% suspension in oil of NaH (0.25 g). After 30 minutes, the mesylate solution was diluted with methylene chloride, washed with NaHCO3 and brine, dried over sodium sulfate and concentrated. This residue was dissolved in DMF (5 mL) and added to the sodium salt of Intermediate 60. The reaction was stirred over the weekend, diluted with ethyl acetate, washed with NaHCO3 and brine, dried over sodium sulfate and concentrated to give the product.

Aufarbeitung

  1. washwashed with NaHCO3 and brine
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated
  4. dissolutionThis residue was dissolved in DMF (5 mL)
  5. additionadded to the sodium salt of Intermediate 60
  6. additiondiluted with ethyl acetate
  7. washwashed with NaHCO3 and brine
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated
  10. customto give the product

Quellen und Nachweise

ORD-Eintrag
ord-e0876a9909fe441ebfdc0dff6c1ed139
Quelldatensatz
uspto-grants-2011_01
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US07875715B2

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