반응 #1055877

반응 방정식

EDC

HOBt

Et3N

4-(2-chloro-5-fluoropyrimidin-4-yl)-benzoic acid methyl ester

LiOH

THF

→

4-(2-chloro-5-fluoropyrimidin-4-yl)-N-[1-(3-chlorophenyl)-2-hydroxyethyl]-benzamide

수율 55.0%

용매

ethyl acetate

H2O

반응 조건

후처리

1. 1
   추출The reaction mixture was extracted with ethyl acetate (10 mL)
2. 2
   기타to remove any byproduct
3. 3
   여과the resulting precipitate filtered
4. 4
   workup.ADDITIONTo a suspension of these solids in 5 mL of DMF
5. 5
   workup.STIRRINGstirred for 10 minutes
6. 6
   workup.STIRRINGthe reaction stirred overnight
7. 7
   workup.WAITAfter 18 hours
8. 8
   세척washed with 1N HCl, NaHCO3, saturated NaCl
9. 9
   농축The organic layer was concentrated
10. 10
    기타the residue purified by chromatography (Silica, 40% ethyl acetate in hexanes)

실험 절차

To a solution of 4-(2-chloro-5-fluoropyrimidin-4-yl)-benzoic acid methyl ester (0.3 g, 1.13 mmol) in 4 mL of THF was added a solution of LiOH (0.378 g, 9.0 mmol) in 4 mL of H2O and stirred at room temperature for 3 hours. The reaction mixture was extracted with ethyl acetate (10 mL) to remove any byproduct. The aqueous layer was acidified to pH=3 with 6N HCl and the resulting precipitate filtered. To a suspension of these solids in 5 mL of DMF was added EDC (0.26 g, 1.36 mmol), HOBt (0.229 g, 1.70 mmol), and Et3N (0.236 mL, 1.70 mmol) and stirred for 10 minutes. (S)-(+)-3-chlorophenyl glycinol (0.353 g, 1.70 mmol) was added and the reaction stirred overnight. After 18 hours, the reaction was diluted with ethyl acetate and washed with 1N HCl, NaHCO3, saturated NaCl. The organic layer was concentrated and the residue purified by chromatography (Silica, 40% ethyl acetate in hexanes) to afford 4-(2-chloro-5-fluoropyrimidin-4-yl)-N-[1-(3-chlorophenyl)-2-hydroxyethyl]-benzamide (0.15 g, 55%) as a white solid. 1H NMR (CDCl3, 500 MHz): 8.40 (d, 1H), 8.15 (d, 2H), 7.90-7.95 (m, 2H), 7.32 (s, 1H), 7.22-7.29 (m, 2H), 7.05-7.08 (m, 1H), 5.18-5.22 (m, 1H), 3.95-4.00 (m, 2H), 1.80 (s, 2H). LCMS: ES+=406.

출처