Isobutylene oxide → 4-{[(2,4-Dichloro-thiazol-5-yl)methyl]-(2-hydroxy-2-methyl-propyl)-amino}-piperidine-1-carboxylic acid tert-butyl ester

HRID 2111936Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2111936
[CH3:1][C:2]1([CH3:5])[CH2:4][O:3]1.Cl([O-])(=O)(=O)=O.[Li+].[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][CH:22]([NH:25][CH2:26][C:27]2[S:31][C:30]([Cl:32])=[N:29][C:28]=2[Cl:33])[CH2:21][CH2:20]1)=[O:18])([CH3:15])([CH3:14])[CH3:13].C(=O)(O)[O-].[Na+]>C(#N)C>[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][CH:22]([N:25]([CH2:26][C:27]2[S:31][C:30]([Cl:32])=[N:29][C:28]=2[Cl:33])[CH2:1][C:2]([OH:3])([CH3:5])[CH3:4])[CH2:21][CH2:20]1)=[O:18])([CH3:15])([CH3:13])[CH3:14]

Komponenten

6

Edukt 4

HCID 11208Isobutylene oxideHCID 516892Sodium BicarbonateHCID 23665649Lithium perchlorateHCID 685747814-{[(2,4-Dichloro-thiazol-5-yl)methyl]-amino}-piperidine-1-carboxylic acid t-butyl ester

Produkt 1

HCID 685774114-{[(2,4-Dichloro-thiazol-5-yl)methyl]-(2-hydroxy-2-methyl-propyl)-amino}-piperidine-1-carboxylic acid tert-butyl esterAusbeute 33,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel2×

Versuchsvorschrift

Add 2,2-dimethyl-oxirane (3.0 mL, 33.3 mmol) to a stirred suspension of lithium perchlorate (3.39 g, 31.9 mmol) in anhydrous acetonitrile (40 mL). Stir for one hour under nitrogen at room temperature. Add 4-{[(2,4-dichloro-thiazol-5-yl)methyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester (1.1337 g, 3.10 mmol) in anhydrous acetonitrile (15 mL). Heat the reaction at reflux for 72 hours under nitrogen. Pour the reaction into saturated sodium bicarbonate (100 mL) and extract with ethyl acetate (3×100 mL). Dry the ethyl acetate over sodium sulfate and then filter off the sodium sulfate. Concentrate on a rotary evaporator and purify the crude product by flash chromatography on silica gel eluting with 30% ethyl acetate/hexanes to yield 0.4527 g (33%) of 4-{[(2,4-dichloro-thiazol-5-yl)methyl]-(2-hydroxy-2-methyl-propyl)-amino}-piperidine-1-carboxylic acid tert-butyl ester: mass spectrum (ion spray): m/z=438.2 (M+1); 1H NMR (CDCl3): δ=4.22 (br s, 2H), 3.97 (s, 2H), 2.67-2.59 (m, 3H), 2.50 (s, 2H), 1.77-1.74 (m, 2H), 1.60 (s, 2H), 1.49 (s, 9H), 1.47-1.35 (m, 1H), 1.23 (s, 6H).

Aufarbeitung

  1. temperatureHeat
  2. customthe reaction
  3. temperatureat reflux for 72 hours under nitrogen
  4. additionPour
  5. extractionextract with ethyl acetate (3×100 mL)
  6. dry with materialDry the ethyl acetate over sodium sulfate
  7. filtrationfilter off the sodium sulfate
  8. concentrationConcentrate on a rotary evaporator
  9. custompurify the crude product by flash chromatography on silica gel eluting with 30% ethyl acetate/hexanes

Quellen und Nachweise

ORD-Eintrag
ord-b8b90998318b4319b1a38f3e24761d41
Quelldatensatz
uspto-grants-2009_04
Patentnummer
US07521462B2

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