Citric Acid → (S)-2-(tert-butyldimethylsilyloxy)-3-ethoxy-N-(5-methylpyridin-2-yl)propanamide

HRID 1098123Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1098123
C[Al](C)C.[CH3:5][C:6]1[CH:7]=[CH:8][C:9]([NH2:12])=[N:10][CH:11]=1.[Si:13]([O:20][C@@H:21]([CH2:26][O:27][CH2:28][CH3:29])[C:22](OC)=[O:23])([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1(C)C=CC=CC=1.O>[Si:13]([O:20][C@@H:21]([CH2:26][O:27][CH2:28][CH3:29])[C:22]([NH:12][C:9]1[CH:8]=[CH:7][C:6]([CH3:5])=[CH:11][N:10]=1)=[O:23])([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14]

Komponenten

7

Edukt 4

HCID 311Citric AcidHCID 153482-Amino-5-methylpyridineHCID 16682925TrimethylaluminumHCID 57438643(S)-methyl 2-(tert-butyldimethylsilyloxy)-3-ethoxypropanoate

Produkt 1

HCID 57504607(S)-2-(tert-butyldimethylsilyloxy)-3-ethoxy-N-(5-methylpyridin-2-yl)propanamideAusbeute 65,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 1140TolueneLösungsmittel2×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A solution of trimethylaluminium (2M in hexane, 2.75 mL, 5.49 mmol) was added dropwise to a stirred solution of 5-methylpyridin-2-amine (0.594 g, 5.49 mmol) in toluene (10 mL) cooled to 0° C., over a period of 5 minutes under nitrogen. The resulting solution was stirred for 15 minutes. A solution of (S)-methyl 2-(tert-butyldimethylsilyloxy)-3-ethoxypropanoate (Intermediate G3) (1.31 g, 4.99 mmol) in toluene (5 mL) was added dropwise over a period of 2 minutes. The resulting solution was allowed to warm to ambient temperature and then heated to reflux for 7 hours then allowed to cool to room temperature and 1M citric acid (20 mL) added, diluted with water (25 mL) and the mixture extracted with ethyl acetate (25 mL). The aqueous was re-extracted with ethyl acetate (25 mL), the organic phases combined, washed with water (5 mL) and brine (20 mL), dried over MgSO4, filtered and evaporated. The residue was purified by flash silica chromatography, elution gradient 10 to 100% EtOAc in isohexane to give (2S)-2-(tert-butyl-dimethylsilyl)oxy-3-ethoxy-N-(5-methylpyridin-2-yl)propanamide (1.1 g, 65%). 1H NMR (400 MHz, CDCl3) δ 0.18 (3H, s), 2.00 (3H, s), 0.99 (9H, s), 1.18 (3H, t), 2.30 (3H, s), 3.51-3.61 (2H, m), 3.63-3.67 (1H, m), 3.78-3.81 (1H, m), 4.41-4.43 (1H, m), 7.51 (1H, dd), 8.13-8.18 (2H, m), 9.03 (1H, s); m/z (ESI+) (M+H)+=339; HPLC tR=3.31 min.

Aufarbeitung

  1. temperatureto warm to ambient temperature
  2. temperatureheated
  3. temperatureto reflux for 7 hours
  4. temperatureto cool to room temperature
  5. extractionthe mixture extracted with ethyl acetate (25 mL)
  6. extractionThe aqueous was re-extracted with ethyl acetate (25 mL)
  7. washwashed with water (5 mL) and brine (20 mL)
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. customevaporated
  11. customThe residue was purified by flash silica chromatography, elution gradient 10 to 100% EtOAc in isohexane

Quellen und Nachweise

ORD-Eintrag
ord-205d20908d104bca98748bf455dd1ed3
Quelldatensatz
uspto-grants-2012_03
Patentnummer
US08143263B2

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