反応 #350564

反応方程式

HCl

3-Morpholinecarboxylic acid

4-chloro-2-fluoro-5-(1-methylethoxy)aniline

trimethylaluminum

→

title compound

収率 43.5%

N-[4-Chloro-2-fluoro-5-(1-methylethoxy)phenyl]morpholine-3-carboxamide

収率 43.5%

溶媒

CH2Cl2

反応条件

後処理

1. 1
   その他The resultant reaction mixture
2. 2
   workup.STIRRINGwas stirred at room temperature for 2 days
3. 3
   その他The solid formed
4. 4
   ろ過was filtered off
5. 5
   workup.ADDITION400 mL of CH2Cl2 was added
6. 6
   その他The organic layer was separated
7. 7
   乾燥dried over MgSO4
8. 8
   その他the solvent was removed under vacuum

実験手順

To a stirring solution of 4-chloro-2-fluoro-5-(1-methylethoxy)aniline (15.52 g, 76.26 mmol) in CH2Cl2 (100 mL), under nitrogen at 0° C. (ice-bath) was added dropwise trimethylaluminum (114.4 mL, 228.78 mmol). The mixture was then stirred overnight at room temperature. 3-Morpholinecarboxylic acid (10.0 g, 76.20 mmol) was added portionwise at room temperature. The resultant reaction mixture was stirred at room temperature for 2 days. 6N HCl was added dropwise to the reaction mixture at 0° C. (ice-bath). The solid formed was filtered off and suspended in water (100 mL). The suspension was basicified with 50% aqueous NaOH to pH 13. 400 mL of CH2Cl2 was added. The organic layer was separated, dried over MgSO4 and the solvent was removed under vacuum to give the title compound of Step B as a white solid (10.5 g), m.p. 99°-101° C. 1H NMR: δ9.30 (br s,1H), 8.17 (d,1H), 7.14 (d,1H), 4.53 (q,1H), 3.96-3.61 (m,5H), 3.00-3.01 (m,2H), 1.37 (d,6H).

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