반응 #350564

반응 방정식

HCl

3-Morpholinecarboxylic acid

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

trimethylaluminum

→

title compound

수율 43.5%

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

수율 43.5%

용매

CH2Cl2

반응 조건

후처리

1. 1
   기타The resultant reaction mixture
2. 2
   workup.STIRRINGwas stirred at room temperature for 2 days
3. 3
   기타The solid formed
4. 4
   여과was filtered off
5. 5
   workup.ADDITION400 mL of CH2Cl2 was added
6. 6
   기타The organic layer was separated
7. 7
   건조dried over MgSO4
8. 8
   기타the solvent was removed under vacuum

실험 절차

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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