Reaktion #44210

Reaktionsgleichung

O-cyclopropylmethyl-hydroxylamine

4-(2-fluoro-4-methylphenylamino)-1,2,5-trimethyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid ethyl ester

lithium bis(trimethylsilyl)amide

→

desired product

Ausbeute 40.6%

4-(2-fluoro-4-methylphenylamino)-1,2,5-trimethyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid cyclopropylmethoxyamide

Ausbeute 40.6%

Lösungsmittel

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe reaction mixture was warmed to room temperature
2. 2
   Sonstigethe reaction was quenched by addition of a saturated aqueous solution of NaHCO3
3. 3
   Sonstigepartitioned between EtOAc and brine
4. 4
   TrocknenThe combined organic extracts were dried (Na2SO4)
5. 5
   Einengenconcentrated
6. 6
   SonstigePurification by flash column chromatography (30:1 methylene chloride/MeOH)

Vorschrift

O-cyclopropylmethyl-hydroxylamine (0.046 g, 0.527 mmol) was added to a solution of 4-(2-fluoro-4-methylphenylamino)-1,2,5-trimethyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid ethyl ester (0.070 g, 0.211 mmol) in THF (2 mL). The solution was cooled to 0° C. and lithium bis(trimethylsilyl)amide (1.05 mL, 1 M solution in hexanes) was added dropwise. The reaction mixture was warmed to room temperature. After stirring for 1 hour, the reaction was quenched by addition of a saturated aqueous solution of NaHCO3 and partitioned between EtOAc and brine. The aqueous layer was reextracted with EtOAc. The combined organic extracts were dried (Na2SO4) and concentrated. Purification by flash column chromatography (30:1 methylene chloride/MeOH) gave 0.032 g (40%) desired product as a yellow solid; MS ESI (+) m/z 374 (M+1) detected; 1H NMR (400 MHz, CD3OD) δ 6.91 (d,1H), 6.83 (d, 1H), 6.63 (t, 1H), 3.59 (s, 3H), 3.47 (d, 2H), 2.41 (s, 3H), 2.27 (s, 3H), 1.86 (s, 3H) 0.99 (m, 1H) 0.48 (m, 2H) 0.18 (m, 2H). 19F (376 MHz, CD3OD)-132.1 (s, 1F).

Quelle