Reaktion #1723707

Reaktionsgleichung

2-bromo-2-methyl-propanamide

8-hydroxyquinaldine

NaH

Cs2CO3

NaH

→

product

Ausbeute 67.6%

2-hydroxy-N-(8-quinaldinyl)-2-methylpropionamide

Ausbeute 67.6%

Lösungsmittel

dioxane

DMPU

NMP

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGthe resulting mixture was stirred
2. 2
   Temperaturat reflux for 16 h
3. 3
   workup.STIRRINGThe resulting mixture was stirred at 150° C. for 72 h
4. 4
   TemperaturThe reaction was cooled to room temp.
5. 5
   Sonstigepartitioned between water (50 mL) and EtOAc (100 mL)
6. 6
   ExtraktionThe aqueous layer was extracted with EtOAc (100 mL)
7. 7
   Waschenthe combined organics washed with water (50 mL)
8. 8
   Trocknendried (Na2SO4)
9. 9
   Einengenconcentrated to about 3 g of material
10. 10
    SonstigeThe brown oil, the rearrangement product, was chromatographed on silica (200 mL, 4 cm diam. column)
11. 11
    Wascheneluting with 3:7 EtOAc/hexane

Vorschrift

To a solution of 8-hydroxyquinaldine (722 mg, 3.70 mmol) in dioxane (20 mL) was added NaH (Aldrich, dry, 300 mg, 12.2 mmol) and Cs2CO3 (4.00 g, 12.2 mmol). The resulting mixture was stirred at room temperature for about 30 minutes, then 2-bromo-2-methyl-propanamide (2.03 g, 12.2 mmol) was added and the resulting mixture was stirred at reflux for 16 h. After the reflux period, NMP (20 mL), DMPU (2 mL), and NaH (Aldrich, dry, 100 mg, 4.07 mmol) were added. The resulting mixture was stirred at 150° C. for 72 h. The reaction was cooled to room temp., and partitioned between water (50 mL) and EtOAc (100 mL). The aqueous layer was extracted with EtOAc (100 mL) and the combined organics washed with water (50 mL), dried (Na2SO4), and concentrated to about 3 g of material. The brown oil, the rearrangement product, was chromatographed on silica (200 mL, 4 cm diam. column), eluting with 3:7 EtOAc/hexane to obtain the product as an off-white solid (610 mg, 2.50 mmol, 67.6% yield).: mp 143-144° C.: 1H NMR (300 MHz, CDCl3) δ10.99 (br s, 1 H, N--H), 8.76-8.73 (m, 1 H), 8.03 (d, 1 H, J=8.26), 7.48-7.45 (om's, 2 H), 7.32 (d, 1 H, J=9.21), 2.80 (br s, 1 H, O--H), 2.75 (s, 3 H, Ar--CH3), 1.62 (s, 6 H, C(CH3)2); 13C NMR (75 MHz, CDCl3) δ174.9, 157.4, 138.2, 136.3, 133.5, 126.2, 126.1, 122.4, 121.6, 116.3, 74.2, 28.1, 25.4; MS (CI/NH3) 245; Analysis: Calculated C 68.83, H 6.60, N 11.47; Found C 68.78, H 6.56, N 11.37.

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